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1.
Medicine (Baltimore) ; 98(40): e17359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577731

RESUMO

INTRODUCTION: The clinical and genetic characteristics of nephrogenic diabetes insipidus (NDI) were described via assessing 2 cases of NDI patients from a Chinese family. PATIENT CONCERNS: Two patients who manifest polyuria and polydipsia were admitted to hospital for definite diagnosis. DIAGNOSIS: Water deprivation-vasopressin tests showed that the patients may possess renal-origin diabetes insipidus. All the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulation hormone, adrenocorticotropic hormone, prolactin, and growth hormone in both patients were normal. These results were certified that both patients possess a nephropathy-type diabetes insipidus. B-mode ultrasonography and urinalysis test demonstrated that the patient's diabetes insipidus is unlikely to originate from renal organic disease. Remarkably, by nucleotide sequencing, we found a novel mutation c.414_418del in arginine-vasopressin receptor 2 (AVPR2) was related to the disease of NDI. INTERVENTIONS: Two patients were treated with oral hydrochlorothiazide and indomethacin. In addition, low salt diet and potassium supplementation throughout the patients' treatment. OUTCOMES: The clinical symptoms of 2 patients were significantly reduced after targeted therapy. CONCLUSION: A mutation in AVPR2 was discovered to be associated with NID. It provides a new target for molecular diagnosis of NDI, enabling families to undergo genetic counseling and obtain prenatal diagnoses.


Assuntos
Diabetes Insípido Nefrogênico/genética , Receptores de Vasopressinas/genética , Grupo com Ancestrais do Continente Asiático , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/tratamento farmacológico , Humanos , Hidroclorotiazida/uso terapêutico , Indometacina/uso terapêutico
2.
J Pediatr Endocrinol Metab ; 32(8): 915-920, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271558

RESUMO

Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Diabetes Insípido Nefrogênico/genética , Diabetes Insípido Nefrogênico/patologia , Proteínas Ativadoras de GTPase/genética , Deleção de Genes , Doenças Genéticas Ligadas ao Cromossomo X/genética , Receptores de Vasopressinas/genética , Éxons , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Lactente , Masculino , Linhagem , Prognóstico
3.
Pan Afr Med J ; 32: 210, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31312322

RESUMO

Disorders of water balance are a disease commonly encountered in our clinical practice. Analysis of vasopressin receptor type II (V2R) is essential to understand the physiology of water balance and it is used as a biological prototype of G protein-coupled receptors (GPCRs). Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a syndrome of inappropriate antidiuretic hormone secretion (SIADH) with low plasmatic vasopressin. The evidence on the role of V2 receptor and of aquaporin (AQP) in the mechanism of action for antidiuretic hormone (ADH) was based on the identification of protein gene mutations in patients with nephrogenic diabetes insipidus and NSIAD syndrome. V2R activating mutations were found in patients with NSIAD, contrasting with the numerous V2R inactivating mutations related to X-linked mutations described in patients with nephrogenic diabetes insipidus.


Assuntos
Diabetes Insípido Nefrogênico/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Síndrome de Secreção Inadequada de HAD/fisiopatologia , Receptores de Vasopressinas/genética , Aquaporinas/metabolismo , Diabetes Insípido Nefrogênico/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Síndrome de Secreção Inadequada de HAD/genética , Mutação , Neurofisinas/metabolismo , Precursores de Proteínas/metabolismo , Receptores de Vasopressinas/metabolismo , Vasopressinas/sangue , Vasopressinas/metabolismo
4.
EBioMedicine ; 44: 574-581, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31175056

RESUMO

BACKGROUND: Pre-eclampsia is a leading cause of maternal mortality and morbidity. Although the exact mechanisms that cause pre-eclampsia remain unclear, it is undeniable that abnormal placental function and circulation are a center for initiation pre-eclampsia. As a potent vasoconstrictor, arginine vasopressin (AVP) has long been implicated in controlling placental vascular tone and circulation; its secretion is grossly elevated in pre-eclamptic circulation. However, little is known about the reactivity of AVP in pre-eclamptic placental vasculature. METHODS: To reveal the special features of placental vascular regulations with placental pathophysiological changes, as well as the corresponding molecular mechanisms under pre-eclamptic conditions, vascular function and molecular assays were conducted with placental vessel samples from normal and pre-eclamptic pregnancies. FINDINGS: The present study found that vasoconstriction responses of placental vessels to AVP were attenuated in pre-eclampsia as compared to in normal pregnancy. The insensitivity of AVP was correlated with the down-regulated AVP receptor 1a (AVPR1A, AVPR1A gene) and protein kinase C isoform ß (PKCß, PKCΒ gene), particularly the hyper-methylation-mediated AVPR1A and PKCΒ gene down-regulation, respectively. INTERPRETATION: The findings collectively revealed that aberrant DNA methylation-mediated gene expressions are correlated with vascular dysfunction in pre-eclamptic placental circulation. FUND: This work was supported by National Nature & Science Foundation of China. "333 Project", "Six one project", "Shuang Chuang Tuan Dui" and Key Discipline "Fetal medicine" of Jiangsu Province, and the Suzhou city "Wei Sheng Ren Cai" program.


Assuntos
Arginina Vasopressina/farmacologia , Metilação de DNA , Resistência a Medicamentos/genética , Placenta/irrigação sanguínea , Placenta/efeitos dos fármacos , Pré-Eclâmpsia/etiologia , Proteína Quinase C beta/genética , Receptores de Vasopressinas/genética , Arginina Vasopressina/uso terapêutico , Ilhas de CpG , Feminino , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/metabolismo , Gravidez , Regiões Promotoras Genéticas , Proteína Quinase C beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico
5.
Brain Behav ; 9(6): e01289, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31090198

RESUMO

INTRODUCTION: In humans, satisfying sexual activity within a pair-bond plays a significant role in relationship quality and maintenance, beyond reproduction. However, the neural and genetic correlates for this basic species-supporting function, in response to a pair-bonded partner, are unknown. METHODS: We examined the neural correlates of oxytocin- (Oxtr rs53576) and vasopressin- (Avpr1a rs3) receptor genotypes with sexual satisfaction and frequency, among a group of individuals in pair-bonds (M relationship length = 4.1 years). Participants were scanned twice (with functional MRI), about 1-year apart, while viewing face images of their spouse and a familiar, neutral acquaintance. RESULTS: Sex satisfaction scores showed significant interactions with Oxtr and Avpr variants associated with social behaviors in a broad network of regions involved in reward and motivation (ventral tegmental area, substantia nigra [SN], and caudate), social bonding (ventral pallidum), emotion and memory (amygdala/hippocampus), hormone control (hypothalamus); and somatosensory and self-other processing (SII, frontal, and temporal lobe). Sexual frequency interactions also showed activations in the SN and paraventricular hypothalamus for Avpr, and the prefrontal cortex for Oxtr. CONCLUSIONS: Satisfying sexual activity in pair-bonds is associated with activation of subcortical structures that support basic motivational and physiological processes; as well as cortical regions that mediate complex thinking, empathy, and self-other processes highlighting the multifaceted role of sex in pair-bonds. Oxtr and Avpr gene variants may further amplify both basic and complex neural processes for pair-bond conservation and well-being.


Assuntos
Encéfalo/fisiologia , Heterossexualidade/psicologia , Satisfação Pessoal , Receptores de Ocitocina/genética , Receptores de Vasopressinas/genética , Comportamento Sexual/psicologia , Parceiros Sexuais/psicologia , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Comportamento Sexual/fisiologia , Adulto Jovem
6.
J Am Soc Nephrol ; 30(6): 946-961, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31097611

RESUMO

BACKGROUND: Antagonists of the V1a vasopressin receptor (V1aR) are emerging as a strategy for slowing progression of CKD. Physiologically, V1aR signaling has been linked with acid-base homeostasis, but more detailed information is needed about renal V1aR distribution and function. METHODS: We used a new anti-V1aR antibody and high-resolution microscopy to investigate Va1R distribution in rodent and human kidneys. To investigate whether V1aR activation promotes urinary H+ secretion, we used a V1aR agonist or antagonist to evaluate V1aR function in vasopressin-deficient Brattleboro rats, bladder-catheterized mice, isolated collecting ducts, and cultured inner medullary collecting duct (IMCD) cells. RESULTS: Localization of V1aR in rodent and human kidneys produced a basolateral signal in type A intercalated cells (A-ICs) and a perinuclear to subapical signal in type B intercalated cells of connecting tubules and collecting ducts. Treating vasopressin-deficient Brattleboro rats with a V1aR agonist decreased urinary pH and tripled net acid excretion; we observed a similar response in C57BL/6J mice. In contrast, V1aR antagonist did not affect urinary pH in normal or acid-loaded mice. In ex vivo settings, basolateral treatment of isolated perfused medullary collecting ducts with the V1aR agonist or vasopressin increased intracellular calcium levels in ICs and decreased luminal pH, suggesting V1aR-dependent calcium release and stimulation of proton-secreting proteins. Basolateral treatment of IMCD cells with the V1aR agonist increased apical abundance of vacuolar H+-ATPase in A-ICs. CONCLUSIONS: Our results show that activation of V1aR contributes to urinary acidification via H+ secretion by A-ICs, which may have clinical implications for pharmacologic targeting of V1aR.


Assuntos
Equilíbrio Ácido-Base/efeitos dos fármacos , Receptores de Vasopressinas/efeitos dos fármacos , Vasopressinas/farmacologia , Equilíbrio Ácido-Base/genética , Animais , Células Cultivadas/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Imunofluorescência , Células HEK293/efeitos dos fármacos , Células HEK293/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Imuno-Histoquímica , Túbulos Renais Coletores/citologia , Túbulos Renais Coletores/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ratos Brattleboro , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores de Vasopressinas/genética , Sensibilidade e Especificidade , Urinálise/métodos
7.
Medicine (Baltimore) ; 98(17): e15348, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027113

RESUMO

RATIONALE: X-linked nephrogenic diabetes insipidus (NDI) is a rare inherited disease, and is characterized by renal resistance to arginine vasopressin (AVP). Its diagnosis can be clinically challenging. The application of molecular genetic analysis can provide a rapid and definitive diagnosis. PATIENT CONCERNS: A 75-year-old woman presented with recurrent nausea and vomiting was admitted to the Department of Gastroenterology. The patient had a strong family history of polydipsia and polyuria. Sequencing analysis of the antidiuretic hormone arginine vasopressin receptor 2 (AVPR2) revealed the novel missense mutation p. Trp164Cys (c.492G>G/C) in exon 2. There was a heterozygous mutation in the patient's sister and niece, while there was a mutation in her sons, brother and nephews. The locus is located on the X chromosome Xq28, and its mutation can lead to X linked recessive NDI. The p. Trp164Cys mutation of AVPR2 gene has not been reported in literature before. The mutation was predicted to be probably damaging by several prediction methods, including SIFT and PolyPhen-2. There was no significant abnormal variation in other detection regions of the gene. And there was also no abnormal variation in AVP and AQP2 genes in this family. DIAGNOSIS: X-linked NDI was diagnosed according to the patient's family history and DNA sequencing analysis. INTERVENTIONS AND OUTCOMES: After treated with desmopressin, antiemetic drugs and massive infusion glucose transfusion, the patient's urine volume decreased and electrolyte disturbance was corrected, and the symptoms of nausea and vomiting gradually disappeared. LESSONS: The patients with suspected congenital NDI should undergo genetic sequencing analysis of AVPR2, AVP and AQP2 genes. A definitive diagnosis can benefit patient and avoid unnecessary investigations.


Assuntos
Diabetes Insípido Nefrogênico/genética , Mutação de Sentido Incorreto , Receptores de Vasopressinas/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Diabetes Insípido Nefrogênico/fisiopatologia , Diabetes Insípido Nefrogênico/terapia , Família , Feminino , Humanos , Fenótipo
8.
Am J Physiol Regul Integr Comp Physiol ; 316(6): R735-R750, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916577

RESUMO

The nonapeptide arginine vasotocin (AVT) regulates osmotic balance in teleost fishes, but its mechanisms of action are not fully understood. Recently, it was discovered that nonapeptide receptors in teleost fishes are differentiated into two V1a-type, several V2-type, and two isotocin (IT) receptors, but it remains unclear which receptors mediate AVT's effects on gill osmoregulation. Here, we examined the role of nonapeptide receptors in the gill of the euryhaline Amargosa pupfish (Cyprinodon nevadensis amargosae) during osmotic acclimation. Transcripts for the teleost V1a-type receptor v1a2 were upregulated over fourfold in gill 24 h after transferring pupfish from 7.5 ppt to seawater (35 ppt) or hypersaline (55 ppt) conditions and downregulated after transfer to freshwater (0.3 ppt). Gill transcripts for the nonapeptide degradation enzyme leucyl-cystinyl aminopeptidase (LNPEP) also increased in fish acclimating to 35 ppt. To test whether the effects of AVT on the gill might be mediated by a V1a-type receptor, we administered AVT or a V1-type receptor antagonist (Manning compound) intraperitoneally to pupfish before transfer to 0.4 ppt or 35 ppt. Pupfish transferred to 35 ppt exhibited elevated gill mRNA abundance for cystic fibrosis transmembrane conductance regulator (cftr), but that upregulation diminished under V1-receptor inhibition. AVT inhibited the increase in gill Na+/Cl- cotransporter 2 (ncc2) transcript abundance that occurs following transfer to hypoosmotic environments, whereas V1-type receptor antagonism increased ncc2 mRNAs even without a change in salinity. These findings indicate that AVT acts via a V1-type receptor to regulate gill Cl- transport by inhibiting Cl- uptake and facilitating Cl- secretion during seawater acclimation.


Assuntos
Proteínas de Peixes/metabolismo , Brânquias/metabolismo , Peixes Listrados/metabolismo , Osmorregulação , Receptores de Vasopressinas/metabolismo , Salinidade , Tolerância ao Sal , Vasotocina/metabolismo , Animais , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Cistinil Aminopeptidase/genética , Cistinil Aminopeptidase/metabolismo , Feminino , Proteínas de Peixes/genética , Peixes Listrados/genética , Masculino , Ocitocina/análogos & derivados , Ocitocina/metabolismo , Receptores de Vasopressinas/genética , Água do Mar , Transdução de Sinais , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Regulação para Cima
9.
Nat Protoc ; 14(4): 1084-1107, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30911173

RESUMO

Bioluminescence resonance energy transfer (BRET) is a transfer of energy between a luminescence donor and a fluorescence acceptor. Because BRET occurs when the distance between the donor and acceptor is <10 nm, and its efficiency is inversely proportional to the sixth power of distance, it has gained popularity as a proximity-based assay to monitor protein-protein interactions and conformational rearrangements in live cells. In such assays, one protein of interest is fused to a bioluminescent energy donor (luciferases from Renilla reniformis or Oplophorus gracilirostris), and the other protein is fused to a fluorescent energy acceptor (such as GFP or YFP). Because the BRET donor does not require an external light source, it does not lead to phototoxicity or autofluorescence. It therefore represents an interesting alternative to fluorescence-based imaging such as FRET. However, the low signal output of BRET energy donors has limited the spatiotemporal resolution of BRET imaging. Here, we describe how recent improvements in detection devices and BRET probes can be used to markedly improve the resolution of BRET imaging, thus widening the field of BRET imaging applications. The protocol described herein involves three main stages. First, cell preparation and transfection require 3 d, including cell culture time. Second, image acquisition takes 10-120 min per sample, after an initial 60 min for microscope setup. Finally, image analysis typically takes 1-2 h. The choices of energy donor, acceptor, luminescent substrates, cameras and microscope setup, as well as acquisition modes to be used for different applications, are also discussed.


Assuntos
Transferência Ressonante de Energia de Fluorescência/métodos , Medições Luminescentes/métodos , Imagem Óptica/métodos , Mapeamento de Interação de Proteínas/métodos , Proteínas Recombinantes de Fusão/genética , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Benzenoacetamidas/metabolismo , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Imidazóis/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Plasmídeos/química , Plasmídeos/metabolismo , Pirazinas/metabolismo , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Renilla , Transfecção , beta-Arrestina 2/genética , beta-Arrestina 2/metabolismo
10.
Biochimie ; 158: 191-198, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30677431

RESUMO

Arginine vasopressin (AVP), a peptide secreted from the posterior pituitary, is chiefly regarded as a hormone involved in the regulation of body fluid balance and osmolality. However, recent evidence has revealed that posterior pituitary hormones can exert important actions on endocrine pancreatic function. In the present study, the presence of AVP receptors, namely Avpr1a (V1a), Avpr1b (V1b) and Avpr2 (V2) was demonstrated in murine islets as well as rodent BRIN BD11 and human 1.1B4 beta-cells. Further to this, AVP was shown to induce significant concentration-dependent (10-12 - 10-6 M) increases of insulin release from both rodent and human beta-cells, as well as mouse islets. Insulinotropic actions of AVP were completely annulled by specific V1a or V1b receptor antagonists, and partially abolished by an oxytocin receptor antagonist. In addition, beta-cell insulin secretory actions of AVP were augmented by both IBMX (200 µM) and KCl (30 mM) and linked to significantly increased cAMP production and [Ca2+]i. AVP substantially increased proliferation of rodent and human beta-cells. Moreover, AVP fully protected against cytokine-induced beta-cell apoptosis. AVP had no effect on glucagon secretion. Immunohistochemical examination of beta- and alpha-cells revealed co-expression of AVP with glucagon, and particularly insulin. Finally, administration of AVP in combination with glucose to mice significantly reduced blood glucose, which was associated with increased plasma insulin. These data indicate that AVP possesses novel and potentially important effects on pancreatic endocrine function. Understanding disturbances in islet AVP receptor signalling could reveal insight into the beta-cell defects associated with diabetes.


Assuntos
Arginina Vasopressina/metabolismo , Glucagon/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Receptores de Vasopressinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arginina Vasopressina/genética , Arginina Vasopressina/farmacologia , Linhagem Celular , Glucagon/genética , Humanos , Insulina/genética , Células Secretoras de Insulina/citologia , Camundongos , Receptores de Vasopressinas/genética
11.
Behav Neurosci ; 133(1): 18-31, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30688485

RESUMO

Altruism is an evolutionarily conserved neurobehavioral mechanism for responding to others' needs, even at a cost to the self. It is thought to be rooted in offspring care and is most prominent in kin and close relationships, but also extends to others. We investigated the neural and genetic (OXTR rs53576 and AVPR1a rs3) correlates of altruism (with the Agape scale) in newlywed pair-bonds. Using functional MRI, 18 participants were scanned (T1) while viewing happy or sad face images of the partner; of a stranger; or of a highly familiar, neutral acquaintance (HFN). Thirteen returned for another scan 11 months later (T2), and the additional control of a neutral expression of the partner and stranger was added. At both time points, the right ventral pallidum (VP), ventral tegmental area, and caudate showed significant responses to Partner (romantic) versus HFN images. At T2, altruism scores, OXTR rs53576 G alleles, and AVPR1a rs3 long alleles showed positive correlations with activity in the left VP/accumbens, amygdala, and septum for both Happy and Sad Partner expressions compared to neutral expressions, but not for strangers. However, when the Happy or Sad partner was compared to a Happy or Sad stranger, positive correlations were limited mainly to the amygdala/entorhinal cortex region. This study localized neural correlates of altruism in pair-bonds, including the VP and the amygdala. Also, responsivity in the VP showed increases or decreases as a function of OXTR and AVPR1a variants. These variations may contribute to behavioral heterogeneity and diverse strategies observed in complex social behaviors. In conclusion, the neural and hormonal basis of altruism in pair-bonds may be phylogenetically conserved, yet genetically variable, and promote pair-bond stability and enhance survival and cooperation of the species. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Altruísmo , Encéfalo/fisiologia , Emoções/fisiologia , Receptores de Ocitocina/genética , Receptores de Vasopressinas/genética , Adulto , Mapeamento Encefálico , Empatia/fisiologia , Expressão Facial , Reconhecimento Facial/fisiologia , Feminino , Humanos , Relações Interpessoais , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
12.
Expert Rev Endocrinol Metab ; 14(1): 13-21, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30596344

RESUMO

INTRODUCTION: Hyponatremia is the most frequent electrolyte disorder in hospitalised patients. Acute and severe hyponatremia may be a life-threatening situation. However, also mild and chronic hyponatremia may negatively affect the health status (i.e. gait disturbances, attention deficits, falls and fractures, and bone loss) and may increase the risk of death. Therefore, it is of paramount importance for clinicians to have an in-depth knowledge on this topic, in order to appropriately manage patients affected by hyponatremia. AREAS COVERED: This review will cover different areas related to this electrolyte disorder. Because many pathologic conditions may be associated with hyponatremia, thorough investigations have to be performed in order to establish the underlying etiology. To establish the cause of hyponatremia is of great importance, because an appropriate therapeutic strategy is strictly dependent on a correct diagnosis. A description of the different available therapeutic approaches for the correction of hyponatremia, including vaptans, will follow. EXPERT COMMENTARY: Undoubtedly, the studies that have been published in recent years and the introduction of vaptans in clinical practice have contributed to increase the awareness on hyponatremia among clinicians. Nevertheless, additional studies are needed in order to clarify some partially uncovered areas.


Assuntos
Marcha/fisiologia , Hiponatremia/tratamento farmacológico , Hiponatremia/etiologia , Síndrome de Secreção Inadequada de HAD/diagnóstico , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Conscientização , Diagnóstico Diferencial , Eletrólitos/metabolismo , Feminino , Disparidades nos Níveis de Saúde , Humanos , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Síndrome de Secreção Inadequada de HAD/induzido quimicamente , Síndrome de Secreção Inadequada de HAD/epidemiologia , Masculino , Modelos Animais , Mutação , Ratos , Receptores de Vasopressinas/efeitos dos fármacos , Receptores de Vasopressinas/genética , Tolvaptan/uso terapêutico
13.
Cancer Res Treat ; 51(2): 438-450, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29879760

RESUMO

PURPOSE: Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods: Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo. RESULTS: In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. CONCLUSION: The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging. RESULTS: suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Desamino Arginina Vasopressina/farmacologia , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desamino Arginina Vasopressina/análogos & derivados , Desamino Arginina Vasopressina/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gen Comp Endocrinol ; 279: 12-26, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29964006

RESUMO

Investigations on the role of the reproductive hormones on VT receptor gene expression are lacking in teleosts. Previously we reported that gonadotropin and steroid hormones modulate the secretion and gene expression of brain and ovarian vasotocin (VT) in the catfish Heteropneustes fossilis. In continuation, in the present study we investigated the role of estradiol-17ß (E2), the maturation-inducing steroid (MIS) 17α, 20ß-dihydroxy-4-pregnen-3-one (17, 20ß-DP), and human chorionic gonadotropin (hCG) on the expression of VT receptor genes (v1a1, v1a2 and v2a) in the brain and ovary of the catfish in early (previtellogenic, preparatory) and late (post vitellogenic, prespawning) phases of the ovarian cycle. The steroid treatments (in vivo and in vitro) modulated only the v1a1 and v1a2 expression in both tissues, but not the v2a expression. The E2-induced modulation of the v1a1 and v1a2 gene expression varied with the reproductive phase. In the preparatory phase, E2 up regulated the expression of brain and ovarian v1a1 and v1a2 gene expression, the response varied with the dose and duration. In the prespawning phase, E2 inhibited the expression in a dose- and duration-dependent manner. On the other hand, 17, 20ß-DP up regulated the expression of brain and ovarian v1a1 and v1a2 in both phases, and the response was higher in the prespawning phase and varied with dose and duration. In contrast to the steroid effects, the hCG treatment modulated the expression of all the VT receptor genes only in the prespawning phase and the response varied with dose and duration. The results indicate differential modulatory roles of steroid hormones and hCG on the VT receptor gene expression, to mediate VT's reproductive or osmoregulatory functions. While the hCG effect on v1a type receptor expression may be steroid- dependent, that of v2a expression seems to be steroid-independent.


Assuntos
Encéfalo/metabolismo , Peixes-Gato/genética , Regulação da Expressão Gênica , Ovário/metabolismo , Receptores de Vasopressinas/genética , Animais , Encéfalo/efeitos dos fármacos , Gonadotropina Coriônica/farmacologia , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroxiprogesteronas/farmacologia , Ovário/efeitos dos fármacos , Receptores de Vasopressinas/metabolismo
15.
Behav Brain Res ; 364: 464-468, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29102591

RESUMO

Social interaction between animals is crucial for the survival and life in groups. It is well demonstrated that oxytocin (OT) and vasopressin (AVP) play critical roles in the regulation of social behaviors in mammals, however, other neurotransmitters and hormones are involved in the brain circuitry related to these behaviors. The present study aimed to investigate the gene expression of neurotransmitter receptors in the brain of OT knockout (OTKO) male mice. In this study, we evaluated the expression levels of the OT receptor (Oxtr), AVP receptors 1a and 1b (Avpr1a; Avpr1b), dopamine receptor 2 (Drd2), and the estrogen receptors alpha and beta (Esr1; Esr2) genes in the hippocampus (HPC), olfactory bulb (OB), hypothalamus (HPT) and prefrontal cortex (PFC). AVP gene (Avp) expression was analyzed in the HPT. Gene expression results were discussed regarding to social interaction and sexual behavior findings. Additionally, we analyzed the influence of OT absence on the Avp mRNA expression levels in the HPT. RNA extraction and cDNAs synthesis followed by quantitative polymerase chain reaction were performed for gene expression determination. Results were calculated with the 2-ΔΔCt method. Our main finding was that HPC is more susceptible to gene expression changes due to the lack of OT. OTKOs exhibited decreased expression of Drd2 and Avpr1b, but increased expression of Oxtr in the HPC. In the PFC, Esr2 was increased. In the HPT, there was a reduced Avp expression in the OTKO group. No differences were detected in the OB and HPT. Despite these changes in gene expression, sexual behavior was not affected. However, OTKO showed higher social investigation and lower aggressive performance than wild-type mice. Our data highlight the importance of OT for proper gene expression of neurotransmitter receptors related to the regulation of social interaction in male mice.


Assuntos
Hipocampo/metabolismo , Relações Interpessoais , Ocitocina/metabolismo , Agressão/fisiologia , Animais , Expressão Gênica/genética , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Knockout , Bulbo Olfatório/metabolismo , Ocitocina/fisiologia , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D2/genética , Receptores Estrogênicos/genética , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/genética , Comportamento Social , Transcriptoma/genética , Vasopressinas/metabolismo
16.
Fish Physiol Biochem ; 45(3): 885-905, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30506436

RESUMO

In the catfish Heteropneustes fossilis, three vasotocin (VT) receptor subtype genes, v1a1, v1a2, and v2a, were cloned and characterized previously. In the present study, using RNA probes, we localized the distribution of the gene transcripts in the brain-pituitary-gonadal (BPG) axis. The V1a-type receptor, v1a1 and v1a2, genes showed similar and overlapping distribution in the brain. The gene paralogs are distributed in the radial glial cells (RGCs) of the telencephalic ventricle and around the third ventricle in the hypothalamus and thalamus, olfactory tract, nucleus preopticus, nucleus lateralis tuberis, nucleus recessus lateralis and posterioris, nucleus saccus vasculosi, thalamic nuclei, habenular nucleus, habenular commissure, basal part of pineal stalk, accessory pretectal nucleus, optic tectum, corpus and valvula of the cerebellum, and facial and vagal lobes. The V2a receptor gene (v2a) has restricted distribution and is largely confined to the anterior subependymal region of the telencephalon. The localization pattern shows that the V1a-type receptors are distributed in major sensorimotor processing centers and the neuroendocrine/reproductive centers of the brain. In the pituitary, the receptor genes were localized differentially in the three divisions with the V1a-type receptor genes strongly expressed in the rostral pars distalis compared to the v2a paralog. In the ovary, the V1a-type receptor genes were localized in the follicular layer while v2a was localized in the oocyte membrane. In the testis, v1a2 and v2a are densely distributed in the interstitial tissue and seminiferous epithelium but the v1a1 is lowly expressed. The results suggest that the VT receptor genes have an extensive but differential distribution in the BPG axis. Future experimental studies are required to correlate the cellular localizations with specific functions of VT in the BPG axis.


Assuntos
Encéfalo/metabolismo , Peixes-Gato/metabolismo , Gônadas/metabolismo , Hipófise/metabolismo , Receptores de Vasopressinas/genética , Animais , Peixes-Gato/genética , Feminino , Doenças dos Peixes/metabolismo , Regulação da Expressão Gênica/fisiologia , Masculino , Ovário/metabolismo , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Testículo/metabolismo
17.
Biol Lett ; 14(12)2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518641

RESUMO

The ratio between the second and fourth digits (2D:4D) has been widely used as a proxy for fetal exposure to androgens and has been linked to a number of sociosexual traits in humans. However, the role of genes in this equation remains unknown. Here (N = 474), we test, firstly, for associations between 2D:4D and single-nucleotide polymorphisms (SNPs) in nine neurochemical receptor genes (AR, OXTR, AVPR1A, OPRM1, DRD1/2, ANKK1, 5HTR1A/2A), and secondly, whether digit ratios mediate the relationship between genetic variation and sociosexuality. We demonstrate significant associations between AR, OPRM1 and AVPR1A and 2D:4D. Moreover, mediation analysis indicates that, in women, AR and OPRM1 variation drives digit ratios, which are related positively to impulsivity and, for OPRM1, negatively to romantic relationship quality. Although these findings are subject to multiple testing issues, this study provides preliminary evidence that in women genetic factors may affect both impulsivity and perceived relationship quality through influencing factors indexed by digit ratios.


Assuntos
Dedos/anatomia & histologia , Comportamento Impulsivo , Receptores Androgênicos/genética , Receptores Opioides mu/genética , Receptores de Vasopressinas/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Caracteres Sexuais , Comportamento Social
18.
Physiol Behav ; 197: 37-41, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30290180

RESUMO

Although the involvement of two types of vasopressin (AVP) receptors, v1a and v1b, in neural regulation of social behavior is well documented in rodents, there is no report on combined actions of them in regulation of social behavior. In this study, we investigated behavioral differences between wild-type (WT) and v1a and v1b double knockout (dKO) mice. For this, we measured olfactory preference, sexual behavior with receptive females (four weekly tests) in an enriched large observation cage, and anxiety-like behaviors. No difference between WT and dKO mice was found in olfactory preferences for estrous female odor to male odor. Over all four mating tests, the number of mounts and pursuits after receptive females was significantly greater in dKO mice than in WT mice. In the elevated plus maze and the open field test, dKO mice showed lower anxiety-like behavior than WT mice. Finally, we measured approach behavior to several types of objects, figurines, and caged anestrous or estrous females placed in the open field apparatus. The only difference observed was that dKO mice spent longer in the vicinity of estrous females than did WT mice. These findings suggest that vasopressin receptors are involved in the regulation of sociosexual behavior, presumably partly mediated by emotional responses, in male mice.


Assuntos
Ansiedade/metabolismo , Receptores de Vasopressinas/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Comportamento de Escolha/fisiologia , Ciclo Estral , Comportamento Exploratório/fisiologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Percepção Olfatória/fisiologia , Receptores de Vasopressinas/genética
19.
Bull Exp Biol Med ; 165(5): 660-664, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30225699

RESUMO

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Cardiotônicos/farmacologia , Oclusão Coronária/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Morfolinas/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Animais não Endogâmicos , Ansiolíticos/farmacologia , Biomarcadores/sangue , Oclusão Coronária/genética , Oclusão Coronária/fisiopatologia , Vasos Coronários/cirurgia , Esquema de Medicação , Reposicionamento de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores de Troca do Nucleotídeo Guanina/antagonistas & inibidores , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Peptídeo Natriurético Encefálico/antagonistas & inibidores , Peptídeo Natriurético Encefálico/sangue , Ratos , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo
20.
J Evol Biol ; 31(12): 1794-1802, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30216586

RESUMO

To reproduce, animals have to form pairs and large variations in the degree of mate switching are observed. Extrinsic and intrinsic factors can constrain individual's mate switching. Among intrinsic factors, genes involved in pair-bonding, such as Avpr-1a, receive increasing attention. The length of microsatellites present in the regulatory region of Avpr-1a determines the neural densities and distributions of the vasopressin receptors known to impact pair-bonding behaviours. For the first time, we investigated whether and how the genetic makeup at Avpr-1a, an intrinsic factor, and the social context, an extrinsic factor, experienced by wild Alpine marmot (Marmota marmota) females affect the proportion of extra-pair young. This proportion was positively correlated with the length of their Avpr-1a regulatory region but only when the social constraints were relaxed, that is when mature male subordinates were present. When ignoring the interactive effect between the length of their Avpr-1a regulatory region and the social constraints, the genetic makeup at Avpr-1a was not associated with the proportion of extra-pair young. Under natural conditions, the genetic regulation of pair-bonding could be hidden by extrinsic factors constraining mate choice.


Assuntos
Marmota/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Ecossistema , Feminino , Genótipo , Masculino , Marmota/genética , Repetições de Microssatélites/genética , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo
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