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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1099-1106, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640965

RESUMO

OBJECTIVE: To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL). METHODS: Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (n=25) and sham operation group (n=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of ß-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting. RESULTS: After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 (P < 0.05) and 7 (P < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 (P < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL. CONCLUSIONS: JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.


Assuntos
Arginina Vasopressina/farmacologia , Citoesqueleto/metabolismo , Sistema de Sinalização das MAP Quinases , Neurônios/citologia , Hipófise/lesões , Regeneração , Animais , Apoptose , Hipófise/citologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tubulina (Proteína)/metabolismo
2.
J Biomed Sci ; 26(1): 71, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530276

RESUMO

BACKGROUND: Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms. METHODS: Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 µM), OPC 21268 (0.1 µM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4-6 h. RESULTS: AVP (0.1 and 1 µM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 µM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 µM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 µM) and OPC 21268 (0.1 µM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 µM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 µM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII. CONCLUSIONS: AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.


Assuntos
Arginina Vasopressina/farmacologia , Cálcio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Veias Pulmonares/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Masculino , Miócitos Cardíacos/fisiologia , Veias Pulmonares/fisiologia , Coelhos
3.
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
4.
Biochem Biophys Res Commun ; 511(4): 780-786, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30833075

RESUMO

In septic shock, arginine vasopressin (AVP) is commonly used as a vasopressor to restore blood pressure. Exogenous AVP may have anti-inflammatory effects as well. We investigated whether AVP modulates the effects of tumor necrosis factor-α (TNF-α) in human aortic endothelial cells (HAECs). TNF-α stimulated intercellular adhesion molecule-1 expression, while AVP pretreatment attenuated this effect of TNF-α. Upon treatment with AVP, extracellular Ca2+ entered the cells rapidly through L-type calcium channels, which in turn induced cell surface translocation of a disintegrin and metalloprotease 10 (ADAM10) and ectodomain shedding of tumor necrosis factor receptor 1 (TNFR1). On the other hand, siRNA depletion of ADAM10 suppressed AVP-induced ectodomain shedding of TNFR1 and eliminated the inhibitory effect of AVP against TNF-α. Depletion of oxytocin receptor also abolished AVP-induced extracellular Ca2+ influx, AVP-induced ectodomain shedding of TNFR1 and the inhibitory effect of AVP against TNF-α. These findings suggest that AVP decreases the responsiveness of HAECs to TNF-α by inducing ADAM10-dependent ectodomain shedding of TNFR1. Extracellular Ca2+ influx through L-type calcium channels was essential for ADAM10 activation. This effect of AVP was mediated through the oxytocin receptor.


Assuntos
Arginina Vasopressina/farmacologia , Células Endoteliais/efeitos dos fármacos , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vasoconstritores/farmacologia , Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Aorta/efeitos dos fármacos , Aorta/metabolismo , Cálcio/metabolismo , Linhagem Celular , Células Endoteliais/metabolismo , Humanos , Proteínas de Membrana/metabolismo
5.
PLoS One ; 14(3): e0214336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30893362

RESUMO

Evidence suggests that ethanol-induced hypertension is associated with increased cardiovascular responsiveness to vasopressors in vivo and enhanced reactivity of isolated arteries to vasopressors ex vivo. The underlying mechanisms are not well understood and the contribution of ethanol metabolites to vascular effects induced by ethanol consumption are unclear. Mesenteric resistance arteries were harvested from Sprague-Dawley rats. Pressure myography was utilized to test effects of ethanol, acetaldehyde and phosphatidylethanol on myogenic tone and on vasoconstriction induced by phenylephrine, arginine vasopressin (aVP), endothelin-1 and KCl. Ethanol, acetaldehyde and phosphatidylethanol concentrations were monitored during the experiments. Ethanol concentrations in the vessel bath decreased with a half-life of 25min; acetaldehyde and phosphatidylethanol concentrations remained constant. Pretreatment with ethanol dose-dependently increased the potency of phenylephrine to induce vasoconstriction 4-fold (p<0.01). These effects were comparable when arteries were pre-treated with a single dose of ethanol for 30min and when ethanol concentrations were kept constant during 30min and 60min of pretreatment. While ethanol also dose-dependently increased the potency of aVP to induce vasoconstriction 1.7-fold (p<0.05), it did not affect vasoconstriction induced by endothelin-1 or KCl. Acetaldehyde pre-treatment (30 min) dose-dependently increased the potency of phenylephrine to induce vasoconstriction 2.7-fold (p<0.01) but did not affect other vasoconstrictor responses. Phosphatidylethanol did not affect any vasoconstrictor responses. Ethanol and its metabolites did not affect myogenic tone. These data suggest that ethanol and acetaldehyde selectively sensitize intrinsic constrictor responses upon activation of vascular α1-adrenergic and/or vasopressin receptors at clinically relevant concentrations. Our findings support the concept that enhanced vasoreactivity to vasoactive hormones contributes to the development of hypertension induced by ethanol consumption. Ex vivo exposure of resistance arteries to ethanol and acetaldehyde resembles effects of chronic ethanol consumption on intrinsic vascular function, and thus could serve as test platform to evaluate interventions aimed to mitigate vascular effects associated with ethanol consumption.


Assuntos
Etanol/farmacologia , Artérias Mesentéricas/fisiologia , Resistência Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Acetaldeído/farmacologia , Animais , Arginina Vasopressina/farmacologia , Endotelina-1/farmacologia , Etanol/química , Glicerofosfolipídeos/farmacologia , Masculino , Artérias Mesentéricas/química , Artérias Mesentéricas/efeitos dos fármacos , Miografia , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Vasoconstrição
6.
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
7.
Am J Physiol Renal Physiol ; 316(4): F743-F757, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30623725

RESUMO

Chronic adenine feeding is extensively used to develop animal models of chronic renal failure with metabolic features resembling those observed in humans. However, the mechanism by which adenine induces renal failure is poorly understood. In this study, we examined the early effects of adenine on water metabolism and salt balance in rats placed in metabolic cages and fed control or adenine-containing diets for 7 days. Molecular and functional studies demonstrated that adenine-fed rats exhibited a significant reduction in food intake, polyuria, polydipsia, decreased urine osmolality, and increased salt wasting. These effects are independent of changes in food intake and result from a coordinated downregulation of water channel aquaporin-2 (AQP2) and salt transporter (Na+-K+-Cl- cotransporter 2; NKCC2) in the collecting duct and medullary thick ascending limb, respectively. As a result, adenine-fed rats exhibited massive volume depletion, as indicated by a significant body weight loss, increased blood urea nitrogen, and increased hematocrit and hemoglobin levels, all of which were significantly corrected with NaCl replacement. Adenine-induced urinary concentrating defect was not corrected by exogenous arginine vasopressin (AVP), and it correlated with reduced cAMP production in vivo and in vitro. In conclusion, adenine acts on renal tubules as a signaling molecule and causes nephrogenic diabetes insipidus with salt wasting, at least, by directly interfering with AVP V2 receptor signaling with subsequent downregulation of NKCC2 and AQP2 in the kidney. The combination of renal fluid loss and decreased food intake with subsequent massive volume depletion likely plays an important role in the development of early prerenal failure that progresses to chronic kidney disease in long-term adenine feeding.


Assuntos
Adenina/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Rim/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Aquaporina 2/antagonistas & inibidores , Arginina Vasopressina/farmacologia , AMP Cíclico/metabolismo , Dieta , Relação Dose-Resposta a Droga , Ingestão de Alimentos , Rim/patologia , Nefropatias/patologia , Masculino , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio/farmacologia , Membro 1 da Família 12 de Carreador de Soluto/antagonistas & inibidores , Água/metabolismo , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
8.
Br J Pharmacol ; 175(16): 3394-3406, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29859008

RESUMO

BACKGROUND AND PURPOSE: Development of combination therapies has received significant interest in recent years. Previously, a two-receptor one-transducer (2R-1T) model was proposed to characterize drug interactions with two receptors that lead to the same phenotypic response through a common transducer pathway. We applied, for the first time, the 2R-1T model to characterize the interaction of noradrenaline and arginine-vasopressin on vasoconstriction and performed inter-species scaling to humans using this mechanism-based model. EXPERIMENTAL APPROACH: Contractile data were obtained from in vitro rat small mesenteric arteries after exposure to single or combined challenges of noradrenaline and arginine-vasopressin with or without pretreatment with the irreversible α-adrenoceptor antagonist, phenoxybenzamine. Data were analysed using the 2R-1T model to characterize the observed exposure-response relationships and drug-drug interaction. The model was then scaled to humans by accounting for differences in receptor density. KEY RESULTS: With receptor affinities set to published values, the 2R-1T model satisfactorily characterized the interaction between noradrenaline and arginine-vasopressin in rat small mesenteric arteries (relative standard error ≤20%), as well as the effect of phenoxybenzamine. Furthermore, after scaling the model to human vascular tissue, the model also adequately predicted the interaction between both agents on human renal arteries. CONCLUSIONS AND IMPLICATIONS: The 2R-1T model can be of relevance to quantitatively characterize the interaction between two drugs that interact via different receptors and a common transducer pathway. Its mechanistic properties are valuable for scaling the model across species. This approach is therefore of significant value to rationally optimize novel combination treatments.


Assuntos
Arginina Vasopressina/farmacologia , Modelos Biológicos , Norepinefrina/farmacologia , Vasoconstrição/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Interações de Medicamentos , Humanos , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Fenoxibenzamina/farmacologia , Ratos Wistar , Artéria Renal/efeitos dos fármacos , Artéria Renal/fisiologia , Biologia de Sistemas
9.
FASEB J ; 32(10): 5520-5531, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29718707

RESUMO

Type-II l-arginine:ureahydrolase, arginase-II (Arg-II), is abundantly expressed in the kidney. The physiologic role played by Arg-II in the kidney remains unknown. Herein, we report that in mice that are deficient in Arg-II (Arg-II-/-), total and membrane-associated aquaporin-2 (AQP2) protein levels were significantly higher compared with wild-type (WT) controls. Water deprivation enhanced Arg-II expression, AQP2 levels, and membrane association in collecting ducts. Effects of water deprivation on AQP2 were stronger in Arg-II-/- mice than in WT mice. Accordingly, a decrease in urine volume and an increase in urine osmolality under water deprivation were more pronounced in Arg-II-/- mice than in WT mice, which correlated with a weaker increase in plasma osmolality in Arg-II-/- mice. There was no difference in vasopressin release under water deprivation conditions between either genotype of mice. Although total AQP2 and phosphorylated AQP2-S256 levels (mediated by PKA) in kidneys under water deprivation conditions were significantly higher in Arg-II-/- mice compared with WT animals, there is no difference in the ratio of AQP2-S256:AQP2. In cultured mouse collecting duct principal mCCDcl1 cells, expression of both Arg-II and AQP2 were enhanced by the vasopressin type 2 receptor agonist, desamino- d-arginine vasopressin (dDAVP). Silencing Arg-II enhanced the expression and membrane association of AQP2 by dDAVP without influencing cAMP levels. In conclusion, in vivo and in vitro experiments demonstrate that Arg-II negatively regulates AQP2 and the urine-concentrating capability in kidneys via a mechanism that is not associated with the modulation of the cAMP pathway.-Huang, J., Montani, J.-P., Verrey, F., Feraille, E., Ming, X.-F., Yang, Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.


Assuntos
Aquaporina 2/metabolismo , Arginase/metabolismo , Túbulos Renais Coletores/metabolismo , Água/metabolismo , Animais , Aquaporina 2/genética , Arginase/genética , Arginina Vasopressina/farmacologia , Linhagem Celular , AMP Cíclico/genética , AMP Cíclico/metabolismo , Túbulos Renais Coletores/citologia , Camundongos , Camundongos Knockout , Receptores de Vasopressinas/agonistas , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo
10.
J Endocrinol ; 237(3): R83-R98, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29555849

RESUMO

Studies over the past decade have challenged the long-held belief that pituitary hormones have singular functions in regulating specific target tissues, including master hormone secretion. Our discovery of the action of thyroid-stimulating hormone (TSH) on bone provided the first glimpse into the non-traditional functions of pituitary hormones. Here we discuss evolving experimental and clinical evidence that growth hormone (GH), follicle-stimulating hormone (FSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) regulate bone and other target tissues, such as fat. Notably, genetic and pharmacologic FSH suppression increases bone mass and reduces body fat, laying the framework for targeting the FSH axis for treating obesity and osteoporosis simultaneously with a single agent. Certain 'pituitary' hormones, such as TSH and oxytocin, are also expressed in bone cells, providing local paracrine and autocrine networks for the regulation of bone mass. Overall, the continuing identification of new roles for pituitary hormones in biology provides an entirely new layer of physiologic circuitry, while unmasking new therapeutic targets.


Assuntos
Tecido Adiposo/metabolismo , Osso e Ossos/metabolismo , Hormônios Hipofisários/fisiologia , Tecido Adiposo/efeitos dos fármacos , Hormônio Adrenocorticotrópico/farmacologia , Hormônio Adrenocorticotrópico/fisiologia , Animais , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Osso e Ossos/efeitos dos fármacos , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/fisiologia , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/fisiologia , Humanos , Ocitocina/farmacologia , Ocitocina/fisiologia , Hormônios Hipofisários/farmacologia , Prolactina/farmacologia , Prolactina/fisiologia , Tireotropina/farmacologia , Tireotropina/fisiologia
11.
Eur J Neurosci ; 47(7): 866-886, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29446159

RESUMO

The preoptic area (POA) of the hypothalamus, containing temperature-sensitive and temperature-insensitive neurons, plays a key role in specific thermoregulatory responses. Although arginine vasopressin (AVP) has been shown to induce hypothermia by increasing the firing activities of warm-sensitive neurons and decreasing those of cold-sensitive and temperature-insensitive neurons, the effects of AVP on POA GABAergic transmission remain unknown. Herein, inhibitory postsynaptic currents (IPSCs) of temperature-sensitive and temperature-insensitive neurons in POA slices were recorded using whole-cell patch clamp. By monitoring changes in GABAergic transmission during AVP treatment, we showed that AVP decreased the amplitudes and frequencies of spontaneous IPSCs in mostly warm-sensitive neurons and in some temperature-insensitive neurons but increased these parameters in other temperature-insensitive neurons. The IPSC amplitude was reduced for only cold-sensitive neurons. RT-PCR and Western blot analyses further confirmed the POA expression of V1a receptors and GABAA receptors, including the subunits α1, α2, α3, ß2, ß3 and γ2. The effects of AVP on IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent on G proteins and intracellular Ca2+ . AVP-mediated modulation was associated with changes in the kinetic parameters (decay time, 10-90% rise time, half-width). Together, these results suggest that AVP, acting via V1a receptors but not V1b receptors, differentially modulates GABAergic synaptic transmission and fine-tunes the firing activities of temperature-sensitive and temperature-insensitive neurons in the rat POA.


Assuntos
Arginina Vasopressina/fisiologia , Neurônios GABAérgicos/fisiologia , Neurônios/fisiologia , Área Pré-Óptica/fisiologia , Transmissão Sináptica/fisiologia , Temperatura Ambiente , Animais , Arginina Vasopressina/farmacologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Ratos , Receptores de GABA-A/biossíntese , Receptores de Vasopressinas/biossíntese
12.
Clin Sci (Lond) ; 132(3): 419-436, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29371289

RESUMO

The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.


Assuntos
Arginina Vasopressina/metabolismo , Pré-Eclâmpsia/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Animais , Arginina Vasopressina/farmacologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neurofisinas/metabolismo , Placenta/efeitos dos fármacos , Placenta/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Precursores de Proteínas/metabolismo , Vasopressinas/metabolismo
13.
Turk Neurosurg ; 28(2): 211-218, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28383092

RESUMO

AIM: To examine morphological, radiological and biochemical effects of arginine vasopressin (AV) and V1 receptor antagonist on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rabbits. MATERIAL AND METHODS: Forty male New Zealand white rabbits were randomly divided into four groups comprising 10 rabbits each. The groups were; 1) Control group, 2) SAH group, 3) SAH+AV group, 4) SAH+V1 antagonist group. Diameters of the basilar artery in all groups were measured on angiograms. All animals were sacrificed two days following basilar angiography and tissue samples of basilar artery were obtained under microscope immediate after craniectomy for ultrastructural and biochemical examinations. RESULTS: The artery diameters were found to be 50% and 50% at the 30th minute in the groups 2 and 3 respectively. In group 3, CVS was 13% more in comparison with the 2nd group. In group 4, vascular constriction was 34.5% at the 30th minute and about 30.9% at the 300th minute. Despite the increase in regional blood flow, AV did not provide morphological change. Histological appearance was related to vascular stenosis due to CVS. Histological outcome was the best in group 4 because of less CVS. CONCLUSION: Arginine vasopressin plays an important role in CVS. We detected morphological and radiological recovery in basilar artery, besides moderate improvement due to AV receptor antagonist in CVS.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Arginina Vasopressina/farmacologia , Artéria Basilar/efeitos dos fármacos , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia , Animais , Modelos Animais de Doenças , Masculino , Coelhos , Distribuição Aleatória , Receptores de Vasopressinas
14.
Front Neuroendocrinol ; 51: 14-24, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29054552

RESUMO

Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological processes. Although the chemical structures of OT and AVP as well as their receptors are quite similar, OT and AVP can have distinct or even opposing actions. Here, we review the increasing body of evidence that exogenously administered and endogenously released OT and AVP can activate each other's canonical receptors (i.e., cross-talk) and examine the possibility that receptor cross-talk following the synaptic and non-synaptic release of OT and AVP contributes to their distinct roles in the brain and periphery. Understanding the consequences of cross-talk between OT and AVP receptors will be important in identifying how these peptides control social cognition and behavior and for the development of drugs to treat a variety of psychiatric disorders.


Assuntos
Arginina Vasopressina/metabolismo , Transtornos Mentais/metabolismo , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Comportamento Social , Animais , Arginina Vasopressina/farmacologia , Feminino , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Ocitocina/farmacologia , Receptores de Ocitocina/efeitos dos fármacos , Receptores de Vasopressinas/efeitos dos fármacos
15.
Neurosci Lett ; 662: 59-64, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28988972

RESUMO

Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E2 (PGE2) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE2 on warm-sensitive neurons, and reversed the excitatory effect of PGE2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V1a receptor antagonist, suggesting that V1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE2-induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE2-induced increase in that in low-slope temperature-insensitive neurons through the V1a receptor. Together, these data indicated that AVP antagonized the PGE2-induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE2-induced change in the prepotential of these neurons in a V1a receptor-dependent manner.


Assuntos
Arginina Vasopressina/farmacologia , Dinoprostona/farmacologia , Neurônios/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Animais , Polaridade Celular , Temperatura Alta , Técnicas In Vitro , Masculino , Neurônios/fisiologia , Técnicas de Patch-Clamp , Área Pré-Óptica/citologia , Ratos Sprague-Dawley
16.
Mol Cell Endocrinol ; 470: 105-114, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28986303

RESUMO

BACKGROUND: Pre-operative detection of corticotropin (ACTH) secreting microadenomas causing Cushing's disease (CD) improves surgical outcomes. Current best magnetic resonance imaging fails to detect up to 40% of these microadenomas. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is specific, but not sensitive in detecting corticotropinomas. Theoretically, secretagogue stimulation with corticotropin releasing hormone (CRH) could improve detection of adenomas with 18F-FDG PET. Previous attempts with simultaneous CRH stimulation have failed to demonstrate increased 18F-FDG uptake in corticotropinomas. We hypothesized that CRH stimulation leads to a delayed elevation in glucose uptake in corticotropinomas. METHODS: Clinical data was analyzed for efficacy of CRH in improving 18FDG-PET detection of corticotropinomas in CD. Glucose transporter 1 (GLUT1) immunoreactivity was performed on surgical specimens. Ex-vivo, viable cells from these tumors were tested for secretagogue effects (colorimetric glucose uptake), and for fate of intracellular glucose (glycolysis stress analysis). Validation of ex-vivo findings was performed with AtT-20 cells. RESULTS: CRH increased glucose uptake in human-derived corticotroph tumor cells and AtT-20, but not in normal murine or human corticotrophs (p < 0.0001). Continuous and intermittent (1 h) CRH exposure increased glucose uptake in AtT-20 with maximal effect at 4 h (p = 0.001). Similarly, CRH and 8-Br-cAMP led to robust GLUT1 upregulation and increased membrane translocation at 2 h, while fasentin suppressed baseline (p < 0.0001) and CRH-mediated glucose uptake. Expectedly, intra-operatively collected corticotropinomas demonstrated GLUT1 overexpression. Lastly, human derived corticotroph tumor cells demonstrated increased glycolysis and low glucose oxidation. CONCLUSION: Increased and delayed CRH-mediated glucose uptake differentially occurs in adenomatous corticotrophs. Delayed secretagogue-stimulated 18F-FDG PET could improve microadenoma detection.


Assuntos
Adenoma Hipofisário Secretor de ACT/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Animais , Arginina Vasopressina/farmacologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Corticotrofos/metabolismo , Dexametasona/farmacologia , Transportador de Glucose Tipo 1/genética , Glicólise/efeitos dos fármacos , Humanos , Camundongos , Transporte Proteico/efeitos dos fármacos , Ovinos , Transcrição Genética/efeitos dos fármacos
17.
J Neural Transm (Vienna) ; 125(1): 103-106, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28821967

RESUMO

The neuropeptides oxytocin and arginine vasopressin (AVP) are involved in the regulation of social behavior and cognition. The current study analyzed the effect of oxytocin and AVP on proliferation and differentiation of serotonergic neurons (RN46A cells). Oxytocin did not affect, while 5-10 µM AVP decreased RN46A proliferation. Oxytocin did not significantly alter, while 10 µM AVP decreased the number of cells extending neurites. We found divergent effects of oxytocin and AVP in serotonergic neurons, underscoring their functional differences.


Assuntos
Arginina Vasopressina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ocitocina/farmacologia , Neurônios Serotoninérgicos/efeitos dos fármacos , Animais , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Relação Dose-Resposta a Droga , Ratos , Neurônios Serotoninérgicos/fisiologia
18.
Am J Physiol Endocrinol Metab ; 315(4): E478-E488, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28174180

RESUMO

Light synchronizes the body's circadian rhythms by modulating the master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. In modern lifestyles that run counter to normal circadian rhythms, the extended and/or irregular light exposure impairs circadian rhythms and, consequently, promotes feeding and metabolic disorders. However, the neuronal pathway through which light is coupled to feeding behavior is less elucidated. The present study employed the light exposure during the dark phase of the day in rats and observed its effect on neuronal activity and feeding behavior. Light exposure acutely suppressed food intake and elevated c-Fos expression in the AVP neurons of SCN and the oxytocin (Oxt) neurons of paraventricular nucleus (PVN) in the hypothalamus. The light-induced suppression of food intake was abolished by blockade of the Oxt receptor in the brain. Retrograde tracer analysis demonstrated the projection of SCN AVP neurons to the PVN. Furthermore, intracerebroventricular injection of AVP suppressed food intake and increased c-Fos in PVN Oxt neurons. Intra-PVN injection of AVP exerted a stronger anorexigenic effect than intracerebroventriclar injection. AVP also induced intracellular Ca2+ signaling and increased firing frequency in Oxt neurons in PVN slices. These results reveal the novel neurocircuit from SCN AVP to PVN Oxt that relays light reception to inhibition of feeding behavior. This light-induced neurocircuit may serve as a pathway for forming the circadian feeding rhythm and linking irregular light exposure to arrhythmic feeding and, consequently, obesity and metabolic diseases.


Assuntos
Arginina Vasopressina/metabolismo , Comportamento Alimentar/fisiologia , Luz , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Arginina Vasopressina/farmacologia , Arginina Vasopressina/fisiologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Ritmo Circadiano/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Masculino , Vias Neurais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ocitocina/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Receptores de Ocitocina , Núcleo Supraquiasmático/fisiologia
19.
Am J Pathol ; 188(1): 173-183, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29128567

RESUMO

The neuropeptides arginine vasopressin (Avp) and vasoactive intestinal polypeptide (Vip) are critical for the communication and coupling of suprachiasmatic nucleus neurons, which organize daily rhythms of physiology and behavior in mammals. However, how these peptides are regulated remains uncharacterized. We found that heterogeneous nuclear ribonucleoprotein U (hnRNP U) is essential for the expression of Avp and Vip. Loss of one copy of the Hnrnpu gene resulted in fragmented locomotor activities and disrupted metabolic rhythms. Hnrnpu+/- mice were more active than wild-type mice in the daytime but more inactive at night. These phenotypes were partially rescued by microinfusion of Avp and Vip into free-moving animals. In addition, hnRNP U modulated Avp and Vip via directly binding to their promoters together with brain and muscle Arnt-like protein-1/circadian locomotor output cycles kaput heterodimers. Our work identifies hnRNP U as a novel regulator of the circadian pacemaker and provides new insights into the mechanism of rhythm output.


Assuntos
Ritmo Circadiano/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/genética , Atividade Motora/genética , Animais , Arginina Vasopressina/genética , Arginina Vasopressina/metabolismo , Arginina Vasopressina/farmacologia , Ritmo Circadiano/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Haploinsuficiência , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia
20.
J Neuroinflammation ; 14(1): 176, 2017 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-28865453

RESUMO

BACKGROUND: Astrocytes support a range of brain functions as well as neuronal survival, but their detailed relationship with stroke-related edema is not well understood. We previously demonstrated that the release of lactate from astrocytes isolated from stroke-prone spontaneously hypertensive rats (SHRSP/Izm) was attenuated under stroke conditions. The supply of lactate to neurons is regulated by astrocytic monocarboxylate transporters (MCTs). The purpose of this study was to examine the contributions of arginine vasopressin (AVP) and/or hypoxia and reoxygenation (H/R) to the regulation of MCTs and neurotrophic factor in astrocytes obtained from SHRSP/Izm and congenic SHRpch1_18 rats. METHODS: We compared AVP-induced lactate levels, MCTs, and brain-derived neurotrophic factor (BDNF) in astrocytes isolated from SHRSP/Izm, SHRpch1_18, and Wistar Kyoto rats (WKY/Izm). The expression levels of genes and proteins were determined by PCR and Western blotting (WB). RESULTS: The production of lactate induced by AVP was increased in astrocytes from all three strains. However, the levels of lactate were lower in SHRSP/Izm and SHRpch1_18 animals compared with the WKY/Izm strain. Gene expression levels of Slc16a1, Slc16a4, and Bdnf were lowered by AVP in SHRSP/Izm and SHRpch1_18 rats compared with WKY/Izm. The increase of MCT4 that was induced by AVP was blocked by the addition of a specific nitric oxide (NO) chelator, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO). Furthermore, AVP increased the expression of iNOS and eNOS proteins in WKY/Izm and SHRSP/Izm rat astrocytes. However, the iNOS expression levels in SHRSP astrocytes differed from those of WKY/Izm astrocytes. The increase of MCT4 protein expression during AVP treatment was blocked by the addition of a specific NF-kB inhibitor, pyrrolidine dithiocarbamate (PDTC). The induction of MCT4 by AVP may be regulated by NO through NF-kB. CONCLUSIONS: These results suggest that the expression of MCTs mediated by AVP may be regulated by NO. The data suggest that AVP attenuated the expression of MCTs in SHRSP/Izm and SHRpch1_18 astrocytes. Reduced expression of MCTs may be associated with decreased lactate production in SHRSP.


Assuntos
Arginina Vasopressina/farmacologia , Astrócitos/metabolismo , Hipertensão/metabolismo , Transportadores de Ácidos Monocarboxílicos/biossíntese , Acidente Vascular Cerebral/metabolismo , Animais , Animais Congênicos , Arginina Vasopressina/fisiologia , Astrócitos/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Expressão Gênica , Hipertensão/genética , Transportadores de Ácidos Monocarboxílicos/genética , Óxido Nítrico/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/genética
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