RESUMO
BACKGROUND: Alcohol is one of the leading threats to health worldwide. Craving for alcohol makes abstinence a difficult challenge by maintaining alcohol dependence. Many studies suppose the hypothalamic-pituitary-adrenal axis, especially the proopiomelanocortin (POMC)-derived neuropeptides, to mediate craving during withdrawal in alcohol dependence. Evidence is available that the two POMC proteins, α-melanocyte-stimulating hormone (α-MSH) and ß-endorphin (ß-END) are altered by alcohol consumption and influence alcohol consumption, respectively. OBJECTIVES: We investigated the dynamics of α-MSH and ß-END during alcohol withdrawal and the influence of intraperitoneal administration of either α-MSH or ß-END in an established rodent model (Wistar rats) for alcohol dependence. RESULTS: After long-term alcohol self-administration over 12 months and repeated deprivation periods for 3 days, we found a significant decrease in α-MSH levels during withdrawal in rodents (p = 0.006) compared to controls, while ß-END levels remained unchanged. Treatment with intraperitoneally administered α-MSH and ß-END did not affect alcohol drinking behavior after deprivation. CONCLUSION: We demonstrate the effects of alcohol deprivation on α-MSH in alcohol-dependent rodents, which appear to mimic α-MSH alteration found after fasting periods during appetite regulation. Therefore, low α-MSH levels are a possible indicator for craving in alcohol-dependent individuals and hence would be a potential target for anti-craving treatment.
Assuntos
Alcoolismo/fisiopatologia , Etanol/administração & dosagem , alfa-MSH/fisiologia , beta-Endorfina/fisiologia , Consumo de Bebidas Alcoólicas , Animais , Modelos Animais de Doenças , Masculino , Ratos Wistar , alfa-MSH/administração & dosagem , alfa-MSH/sangue , beta-Endorfina/administração & dosagem , beta-Endorfina/sangueRESUMO
BACKGROUND: Phospholipase activity and its induction by ß-endorphin have been associated with pathogenic Malassezia pachydermatis animal isolates. OBJECTIVE: To evaluate Malassezia phosholipase activity in human isolates from seborrhoeic dermatitis (SD) and healthy controls before and after ß-endorphin exposure. METHODS: Eighty-four volunteers with or without SD (N = 41) were sampled. Isolated Malassezia strains were incubated in Dixon's medium with and without 100 nmol/L ß-endorphin. Subsequently, phospholipase activity was assessed in egg-yolk agar and the results were compared employing Wilcoxon sign test for paired data, chi-squared test and multinomial logistic regression analysis. RESULTS: A total of 64 Malassezia strains were isolated. SD strains tended to have decreased phospholipase activity before (P = 0.057) and increased after exposure to ß-endorphin (P = 0.061) compared to isolates from healthy skin. Phospholipase activity after ß-endorphin exposure related to basal enzyme activity as a measure of per strain phospholipase inducibility by ß-endorphin did not depend on Malassezia species (P = 0.652). However, this latter biochemical trait discriminates strains isolated from SD lesional and healthy skin (P = 0.036). CONCLUSION: ß-endorphin exposure modifies the in vitro phosholipase activity in Malassezia species isolated from SD lesional skin. This is in accordance with emerging evidence that enhanced local lipase activity is involved in the pathogenesis of SD.
Assuntos
Dermatite Seborreica/microbiologia , Malassezia/isolamento & purificação , Fosfolipases/metabolismo , beta-Endorfina/administração & dosagem , Adulto , Estudos de Casos e Controles , Humanos , Malassezia/classificação , Especificidade da EspécieRESUMO
Intraperitoneal injection of ß-endorphin in doses of 1, 0.01, and 0.0005 µg/kg under conditions of systemic immunization increased the count of antibody-producing cells in the spleen and the titer of anti-erythrocyte antibodies in the plasma of experimental animals. Intraperitoneal ß-endorphin stimulated proliferative activity of splenocytes in mice in the presence of both B- and T-cell mitogen, did not change the production of IFN-γ, reduced the level of IL-2, and stimulated the secretion of IL-4, the main Th2-polarizing factor.
Assuntos
Neurotransmissores/administração & dosagem , Células Th1/efeitos dos fármacos , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , beta-Endorfina/administração & dosagem , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Concanavalina A/farmacologia , Relação Dose-Resposta a Droga , Imunidade Humoral , Injeções Intraperitoneais , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-2/biossíntese , Interleucina-2/imunologia , Interleucina-4/biossíntese , Interleucina-4/imunologia , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Camundongos , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Células Th1/citologia , Células Th1/imunologia , Células Th2/citologia , Células Th2/imunologiaRESUMO
Investigation ofopioid peptide effect on the production of reactive oxygen species by neutrophils in non-fractionated leukocyte suspension and in purified fraction of peripheral blood neutrophils is disclosed in this work. It was determined that selective delta- and micro-agonists of peptide origin stimulated the spontaneous and suppressed 15 mkg/ml zymosan-induced LDCL (luminol-dependent chemiluminescence) reaction of neutrophils in leukocyte suspension. beta-endorphin was found to render less marked suppressive action on 15 mkg/ml zymosan-induced LDCL, and delta2-agonist deltorphin 2 promoted 15 mkg/ml zymosan-induced LDCL only toward the 25 minutes of the experiment. beta-endorphin and selective d- and m- agonists did not affect the spontaneous and suppressed 15 mkg/ml and 150 mkg/ml zymosan-induced neutrophil LDCL. Therefore, opioid peptides play essential role in the process of direct and indirect regulation of oxygen-dependent system of neutrophil granulocyte bactericidal activity.
Assuntos
Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Peptídeos Opioides , Receptores Opioides/agonistas , Zimosan/administração & dosagem , Adulto , Comunicação Celular/fisiologia , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Leucina Encefalina-2-Alanina/farmacologia , Feminino , Humanos , Substâncias Luminescentes/farmacologia , Luminol/farmacologia , Neurotransmissores/administração & dosagem , Oligopeptídeos/administração & dosagem , Peptídeos Opioides/sangue , Espécies Reativas de Oxigênio/sangue , Receptores Opioides/metabolismo , beta-Endorfina/administração & dosagemRESUMO
The present study was performed to characterize the differential molecular mechanisms of morphine and beta-endorphin which are injected intracerebroventiricularly in mice. In the immunoblot assay, the increases of phosphorylated extracellular signal-regulated protein kinase (pERK) as well as phosphorylated calcium/calmodulin-dependent protein kinase IIalpha (pCaMK-IIalpha) expression induced by noxious stimuli were attenuated by intracerebroventricular (i.c.v.) beta-endorphin pretreatment in the hypothalamus, but not by i.c.v. morphine pretreatment. In addition to these immunoblot results, immunohistochemical study also showed that the attenuation of pERK or pCaMK-IIalpha immunoreactivity elicited by i.c.v. pretreatment of beta-endorphin mainly occurred in the paraventricular nucleus of the hypothalamus (PVN). We also investigated the effect of morphine and beta-endorphin on pERK and pCaMK-IIalpha expression in the locus coeruleus (LC). I.c.v. injection of morphine significantly increased pERK as well as pCaMK-IIalpha expression in the locus coeruleus, while beta-endorphin increased only pCaMK-IIalpha in the LC. In addition, beta-endorphin significantly attenuated pERK expression induced by SP i.t. injection. These results suggest that the antinociceptive effects of supraspinally administered morphine and beta-endorphin are involved with differentially intracellular signal transduction molecules-pERK, pCaMK-IIalpha in the PVN and the LC.
Assuntos
Analgésicos Opioides/farmacologia , Química Encefálica/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/biossíntese , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Morfina/farmacologia , Dor/metabolismo , beta-Endorfina/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Western Blotting , Química Encefálica/efeitos dos fármacos , Formaldeído , Imuno-Histoquímica , Injeções Intraventriculares , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Morfina/administração & dosagem , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/fisiologia , Substância P , beta-Endorfina/administração & dosagemRESUMO
The effect of prolonged intermittent infusion of beta-endorphin or naloxone into the third cerebral ventricle in ewes during the follicular phase of the estrous cycle on the expression of GnRH gene and GnRH-R gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland was examined by Real time-PCR. Activation of micro opioid receptors decreased GnRH mRNA levels in the hypothalamus and led to complex changes in GnRH-R mRNA: an increase of GnRH-R mRNA in the preoptic area, no change in the anterior hypothalamus and decrease in the ventromedial hypothalamus and stalk/median eminence. In beta-endorphin treated ewes the levels of GnRH-R mRNA in the anterior pituitary gland also decreased significantly. These complex changes in the levels of GnRH mRNA and GnRH-R mRNA were reflected in the decrease of LH secretion. Blockade of micro opioid receptors affected neither GnRH mRNA and GnRH-R mRNA nor LH levels secretion. These results indicate that beta-endorphin displays a suppressive effect on the expression of the GnRH gene in the hypothalamus and GnRH-R gene in the anterior pituitary gland, but affects GnRH-R gene expression in a specific manner in the various parts of hypothalamus; altogether these events lead to the decrease in GnRH/LH secretion.
Assuntos
Hormônio Liberador de Gonadotropina/genética , Hipotálamo/efeitos dos fármacos , Naloxona/administração & dosagem , Adeno-Hipófise/efeitos dos fármacos , Ovinos/metabolismo , beta-Endorfina/administração & dosagem , Animais , Cruzamento , Ciclo Estral , Feminino , Expressão Gênica/efeitos dos fármacos , Hipotálamo/química , Hormônio Luteinizante/metabolismo , Adeno-Hipófise/química , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Receptores LHRH/genética , Estações do AnoRESUMO
The effects of gonadotropin-releasing hormone (GnRH), beta-endorphin and its antagonist naloxone on the expression of luteinizing hormone (LH) subunit genes and LH secretion were examined in ovariectomized and/or cycling female rats through their direct microinjection into the third cerebral ventricle, in the proximity of the hypothalamus-pituitary complex. GnRH (1 nM) induced a significant augmentation of the pituitary content of alpha mRNA when administered 15, 30 or 60 min intervals over 5 h to ovariectomized rats whereas only the 30 and 60 min intervals were effective in increasing LHbeta mRNA, and the 60 min intervals for LH release. This was in agreement with the established concept of a pulse-dependent regulation of gonadotropin synthesis and release. Hourly pulses of GnRH also increased alpha and LHbeta mRNA levels when microinjected in female cycling rats during proestrus or diestrus II. Using this model we observed a marked negative influence of hourly intracerebral microinjections of beta-endorphin on LH mRNA content and LH release in ovariectomized rats while naloxone had no effect. This suggests that endogenous beta-endorphin was unable to exert its negative action on beta-endorphin receptors that were present and responded to the ligand. The present approach would be valuable for the exploration of the mechanisms of action of beta-endorphin or other substances on the functions of the gonadotrophs.
Assuntos
Ventrículos Cerebrais/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa de Hormônios Glicoproteicos/genética , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/genética , Adeno-Hipófise/fisiologia , beta-Endorfina/farmacologia , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Estro , Feminino , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Hormônio Liberador de Gonadotropina/administração & dosagem , Injeções Intraventriculares , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Microinjeções , Naloxona/administração & dosagem , Naloxona/farmacologia , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Ratos , Ratos Wistar , beta-Endorfina/administração & dosagemRESUMO
CONTEXT: The opioid system is involved in blood pressure regulation in both normal humans and patients with essential hypertension. OBJECTIVE: The objective of the study was to investigate the effects of a high-dose infusion of beta-endorphin, an opioid peptide, on blood pressure and on the hormonal profile in healthy subjects and in hypertensive patients and the mediation played by opioid receptor agonism. DESIGN, SETTING, AND PARTICIPANTS: According to a randomized double-blind design, 11 healthy subjects (controls) and 12 hypertensive inpatients (mean age, 38.9 and 40.4 yr, respectively) received 1-h iv infusion of beta-endorphin (250 mug/h) and, on another occasion, the same infusion protocol preceded by the opioid antagonist naloxone (8 mg). MAIN OUTCOME MEASURES: Hemodynamic and hormonal measurements were performed at established times during the infusion protocols. RESULTS: At baseline, circulating beta-endorphin, norepinephrine, and endothelin-1 in hypertensive patients were significantly (P < 0.05) higher than in controls. In controls, beta-endorphin reduced blood pressure (P < 0.01) and circulating norepinephrine (P < 0.02) and increased plasma atrial natriuretic factor (P < 0.003) and GH (P < 0.0001). In hypertensive patients, beta-endorphin decreased systemic vascular resistance (P < 0.0001), blood pressure (P < 0.0001), and plasma norepinephrine (P < 0.0001) and endothelin-1 (P < 0.0001) and raised circulating atrial natriuretic factor (P < 0.0001), GH (P < 0.0001), and IGF-I (P < 0.0001). These hemodynamic and hormonal responses to beta-endorphin in hypertensive patients were significantly (P < 0.0001) greater than in controls but were annulled in all individuals when naloxone preceded beta-endorphin infusion. CONCLUSIONS: High doses of beta-endorphin induce hypotensive and beneficial hormonal effects in humans, which are enhanced in essential hypertension and are mediated by opioid receptors.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hormônios/sangue , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Receptores Opioides/agonistas , beta-Endorfina/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , beta-Endorfina/uso terapêuticoRESUMO
Among the opioid receptors, which have been pharmacologically classified as mu, delta, kappa and epsilon, the existence of the epsilon receptor has been controversial, and this receptor is generally not recognized as a member of the opioid peptide receptor family because it has not been precisely characterized. However, results from pharmacological, physiological and opioid receptor binding studies clearly indicate the presence of epsilon-opioid receptors, which are distinct from mu-, delta- or kappa-opioid receptors. This putative epsilon-opioid receptor is stimulated supraspinally by the endogenous opioid peptide beta-endorphin, which induces the release of Met-enkephalin, which, in turn, acts on spinal delta2-opioid receptors to produce antinociception. In this article, this beta-endorphin-sensitive epsilon-opioid receptor-mediated descending pain control system, which is distinct from that activated by the mu-opioid receptor agonist morphine, is described and the physiological role of the beta-endorphin-mediated system in pain control activated by cold-water swimming and intraplantar injection of formalin is discussed.
Assuntos
Analgésicos Opioides/farmacologia , Receptores Opioides/fisiologia , beta-Endorfina/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Humanos , Injeções Espinhais , beta-Endorfina/administração & dosagemRESUMO
We have investigated to what extent microinjected beta-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat beta-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for beta-endorphin and mu-opioid receptors. The beta-endorphin injected rats showed a marked increase in beta-endorphin immunoreactive (IR) material in the CSF, with a peak at 30-45 min post-injection, and this beta-endorphin-IR material existed mainly as the intact beta-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct beta-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous beta-endorphin. The beta-endorphin-IR in several of the globus pallidus cell bodies colocalized with the mu-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic beta-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.
Assuntos
Líquido Cefalorraquidiano/química , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Espaço Extracelular/efeitos dos fármacos , beta-Endorfina/líquido cefalorraquidiano , beta-Endorfina/farmacocinética , Animais , Líquido Cefalorraquidiano/fisiologia , Difusão , Espaço Extracelular/metabolismo , Globo Pálido/citologia , Globo Pálido/efeitos dos fármacos , Globo Pálido/metabolismo , Imuno-Histoquímica , Ventrículos Laterais/fisiologia , Masculino , Espectrometria de Massas , Microinjeções , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/efeitos dos fármacos , Receptores Opioides mu/metabolismo , Núcleos Septais/citologia , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Fatores de Tempo , beta-Endorfina/administração & dosagemRESUMO
We examined the effect of the subcutaneous (s.c.) pretreatment of formalin into both hind paws of mice on the antinociception induced by the intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administration of beta-endorphin using the tail-flick test. Pretreatment with formalin (5%) for 5 h had no affect on the i.c.v. administered beta-endorphin-induced tail-flick response. However, pretreatment with formalin for 40 h attenuated the tail-flick inhibition induced by i.c.v. administered beta-endorphin. This antinociceptive tolerance to i.c.v. beta-endorphin continued up to 1 week, but to a lesser extent. Pretreatment with formalin for 5 and 40 h significantly reduced the i.t. beta-endorphin-induced inhibition of the tail-flick response, which continued up to 1 week. The s.c. formalin treatment increased the hypothalamic pro-opiomelanocortin (POMC) mRNA level at 2 h, but this returned to the basal level after 40 h. Our results suggest that the increase in the POMC mRNA level in the hypothalamus appears to be involved in the supraspinal or spinal beta-endorphin-induced antinociceptive tolerance in formalin-induced inflammatory pain.
Assuntos
Formaldeído , Medição da Dor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , beta-Endorfina/antagonistas & inibidores , beta-Endorfina/farmacologia , Animais , Northern Blotting , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraventriculares , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Pró-Opiomelanocortina/biossíntese , Pró-Opiomelanocortina/fisiologia , RNA Mensageiro/biossíntese , beta-Endorfina/administração & dosagemRESUMO
A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeks postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg) at 30-min intervals. Blood samples for LH measurements were withdrawn immediately before and 10 min after each NMDA injection. The results show that intracerebroventricular beta END, IL-1 beta, or NPK inhibited LH release. Multiple injections of NMDA did not alter the existing pattern of LH secretion in castrated control rats. However, similar NMDA injections completely prevented the decrease in LH release by beta END, IL-1 beta, or NPK. Plasma LH levels in these rats remained within the range seen in untreated control rats throughout the 120-min duration of the experiment, and NMDA injections at 30-min intervals evoked pulses of LH that resembled those seen normally in castrated rats. The blockade of the inhibitory effects of the three peptides by NMDA and previous knowledge of hypothalamic sites of NMDA action suggest that EAA systems may represent a common pathway down-stream in the hypothalamic LHRH-regulating circuitry to mediate diminution of LH release by inhibitory peptides. Further, their inhibitory influence may be exerted either directly at the level of LHRH neurons and/or by diminution in EAA efflux, leading to suppression of LHRH and LH release.
Assuntos
Interleucina-1/farmacologia , Hormônio Luteinizante/metabolismo , N-Metilaspartato/farmacologia , Neuropeptídeos/farmacologia , Taquicininas , beta-Endorfina/farmacologia , Animais , Injeções Intraventriculares , Interleucina-1/administração & dosagem , Cinética , Masculino , N-Metilaspartato/administração & dosagem , Neuropeptídeos/administração & dosagem , Ratos , beta-Endorfina/administração & dosagemRESUMO
Endogenous opioid peptides have a role in the regulation of the hypothalamic-pituitary-adrenal axis. Recently, beta-endorphin (EP) has been thought to inhibit CRF release in vivo and in vitro. In the present study we examined the effects of central administration of EP on ACTH secretion and gene expression of both CRF in the hypothalamus and POMC in the anterior pituitary gland (AP) during basal and insulin-induced hypoglycemia in pentobarbital-anesthetized rats. Administration of EP in the lateral ventricle decreased basal CRF levels in the median eminence and inhibited basal and hypoglycemia-induced ACTH secretion in a dose-dependent manner. Hypoglycemia-induced POMC mRNA levels in the AP and CRF mRNA levels in the hypothalamus were also dose-dependently inhibited by the administration of EP. The inhibitory effect of EP was reversed by naloxone. These results suggest that 1) central administration of EP acts through the opioid receptor to inhibit hypoglycemia-induced CRF gene expression in the hypothalamus and CRF release, which results in a decrease in ACTH secretion and POMC mRNA levels in the AP; and 2) the active site of EP is the CRF neuron in the paraventricular nucleus.
Assuntos
Hormônio Liberador da Corticotropina/genética , Expressão Gênica/genética , Hipoglicemia/fisiopatologia , Hipotálamo/química , beta-Endorfina/farmacologia , Hormônio Adrenocorticotrópico/sangue , Animais , Northern Blotting , Hormônio Liberador da Corticotropina/análise , Hormônio Liberador da Corticotropina/sangue , Expressão Gênica/efeitos dos fármacos , Hipotálamo/fisiologia , Injeções Intraventriculares , Masculino , Adeno-Hipófise/química , Pró-Opiomelanocortina/análise , Pró-Opiomelanocortina/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Radioimunoensaio , Ratos , Ratos Endogâmicos , beta-Endorfina/administração & dosagemRESUMO
Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Epinefrina/farmacologia , Obesidade/sangue , beta-Endorfina/farmacologia , Adulto , Glicemia/análise , Peptídeo C/sangue , Epinefrina/administração & dosagem , Epinefrina/sangue , Feminino , Glucagon/sangue , Humanos , Infusões Intravenosas , Insulina/sangue , Masculino , beta-Endorfina/administração & dosagem , beta-Endorfina/sangueRESUMO
It has previously been reported that beta-endorphin, given intraventricularly, releases methionine-enkephalin from the spinal cord in rats. The present studies sought to determine whether beta-endorphin, given supraspinally, also released immunoreactive met-enkephalin from the spinal cord in cats, guinea pigs and mice. Intracerebroventricular injection of beta-endorphin caused a dose-dependent increase of the release of immunoreactive met-enkephalin from the spinal cord in these animals. The results support the hypothesis that the pharmacological actions produced by beta-endorphin are mediated by the release of met-enkephalin.
Assuntos
Encefalina Metionina/metabolismo , Medula Espinal/efeitos dos fármacos , beta-Endorfina/farmacologia , Animais , Gatos , Feminino , Cobaias , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos ICR , Perfusão , Radioimunoensaio , Medula Espinal/metabolismo , beta-Endorfina/administração & dosagemRESUMO
The effects of the intrathecal injection of thiorphan (an inhibitor of enkephalinase inhibitor), bestatin (an inhibitor of aminopeptidase), desipramine (an inhibitor of the uptake of noradrenaline) and fluoxetine (an inhibitor of the uptake of serotonin) on the antinociception induced by beta-endorphin and morphine, administered intracerebroventricularly, were studied in male ICR mice. Antinociceptive effects were assessed by the tail-flick and hot-plate tests. Thiorphan (16 micrograms) and bestatin (16 micrograms), injected intrathecally, potentiated inhibition of the tail-flick response, induced by beta-endorphin but not by morphine administered intracerebroventricularly, whereas desipramine (6 micrograms) and fluoxetine (6 micrograms), injected intrathecally potentiated inhibition of the tail-flick response induced by morphine, but not by beta-endorphin, administered intracerebroventricularly. Thiorphan, bestatin, desipramine or fluoxetine, given intrathecally, did not antagonize inhibition of the hot-plate response, induced by beta-endorphin or morphine administered intracerebroventricularly. The results indicate that inhibition of the tail-flick response, induced by beta-endorphin administered intracerebroventricularly, is mediated by the opioid system, but not by noradrenergic and serotonergic systems in the spinal cord. On the other hand, the inhibition of the tail-flick response, induced by morphine given intracerebroventricularly, is mediated by noradrenergic and serotonergic systems, but not by the opioid system in the spinal cord. The lack of effect of enzyme inhibitors and inhibitors of the uptake of biogenic amines intrathecally on beta-endorphin- and morphine-induced inhibition of the hot-plate response, is due to the supraspinal nature of the nociceptive hot-plate response. The present results further support the hypothesis, proposed previously, that intracerebroventricularly injected beta-endorphin and morphine elicit antinociception by activating different descending inhibitory systems.
Assuntos
Analgésicos , Desipramina/farmacologia , Fluoxetina/farmacologia , Leucina/análogos & derivados , Morfina/farmacologia , Tiorfano/farmacologia , beta-Endorfina/farmacologia , Animais , Injeções Intraventriculares , Injeções Espinhais , Leucina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Morfina/administração & dosagem , Tempo de Reação/efeitos dos fármacos , Tiorfano/administração & dosagem , beta-Endorfina/administração & dosagemRESUMO
Intracerebroventricular injection of beta-endorphin stimulated the metabolism of dopamine in a dose-dependent, opiate antagonist-reversible manner. Local injections into the nucleus accumbens also caused similar increases, indicating that the actions of this peptide on mesolimbic dopaminergic projections were occurring at opioid receptor sites within the nucleus accumbens. Tolerance experiments suggested that epsilon opioid receptors may be involved in mediating these effects in the n. accumbens, unlike in the striatum.
Assuntos
Ventrículos Cerebrais/fisiologia , Corpo Estriado/metabolismo , Dopamina/metabolismo , Núcleo Accumbens/fisiologia , Núcleos Septais/fisiologia , beta-Endorfina/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Encefalina Leucina/análogos & derivados , Encefalina Leucina/farmacologia , Leucina Encefalina-2-Alanina , Ácido Homovanílico/metabolismo , Injeções Intraventriculares , Cinética , Masculino , Morfina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Valores de Referência , beta-Endorfina/administração & dosagemRESUMO
A 100 plaque forming unit (pfu) dose of a temperature-sensitive (ts) mutant of vesicular stomatitis virus (VSV), tsG31 KS5, engendered a slowly progressive paralytic central nervous system (CNS) disease that killed all BALB/c nude mice within 28 days. Reconstitution of nude mice with 10(7) syngeneic splenocytes 24 h before intracerebral inoculation with tsG31 KS5 VSV, however, protected 92% of the animals from death. When these reconstituted animals were injected intracerebroventricularly with 14 pmol of beta-endorphin 24 h after reconstitution with splenocytes and 24 h before inoculation with tsG31 KS5 VSV, only 72% of the animals survived. Furthermore, whereas 40% of the afflicted reconstituted nude mice given intracerebroventricular injections of sterile water were able to recover from the symptoms of disease, those surviving animals which received beta-endorphin were unable to do so. A single intravenous injection of 14 pmol beta-endorphin, or repeated postinfection administration of 28 pmol of beta-endorphin intravenously into nude mice reconstituted with syngeneic splenocytes, which were pretreated with beta-endorphin, did not alter the course of CNS disease induced by tsG31 KS5 VSV. The effect induced by intracerebroventricular injection of beta-endorphin was antagonized by naloxone, but not by the neuropeptide fragment beta-endorphin-(1-27). A simultaneous intracerebroventricular injection of reconstituted nude mice with 1220 pmol of naloxone and 14 pmol of beta-endorphin resulted in a 89% survival rate, and 33% of the afflicted animals were able to overcome the symptoms of the disease induced by tsG31 KS5 VSV. Intracerebroventricular injection of reconstituted nude mice with 330 pmol of beta-endorphin-(1-27) and 14 pmol of beta-endorphin resulted in a 72% survival rate and the surviving animals were unable to improve appreciably the clinical status of their disease. Injection of reconstituted nude mice with either 1220 pmol of naloxone or 330 pmol of beta-endorphin-(1-27) alone did not alter the course of the CNS disease in any way. A single intracerebroventricular injection of 29 pmol of another psychoactive peptide, [Des-Tyr]-endorphin, 24 h after reconstitution of nude mice with splenocytes and 24 h prior to infection with virus, resulted in 74% survival; and 39% of the afflicted animals were able to recover from the clinical symptoms.
Assuntos
Doenças do Sistema Nervoso Central/imunologia , beta-Endorfina/fisiologia , Animais , Doenças do Sistema Nervoso Central/microbiologia , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Baço/citologia , Baço/transplante , Temperatura , Vírus da Estomatite Vesicular Indiana/patogenicidade , beta-Endorfina/administração & dosagem , beta-Endorfina/análogos & derivadosRESUMO
A single intracerebroventricular (i.c.v.) injection of 14 pmol of beta-endorphin into 6-7-week-old BALB/c (+/+) donor mice, 24 h prior to isolation of their T lymphocytes for use for reconstitution of athymic BALB/c (nu/nu) nude mice, altered the immuno-protective effect of adoptive transfer against an intracerebral (i.c.) infection with a temperature-sensitive mutant of vesicular stomatitis virus (tsG31 KS5 VSV). Simultaneous injection of beta-endorphin and naloxone into donor animals negated the opiate effects on splenic lymphocytes. T lymphocytes, isolated from beta-endorphin-treated donors, and then depleted with anti-asialo GM1 antiserum and complement failed to demonstrate the detrimental effects of beta-endorphin.
Assuntos
Linfócitos T/transplante , beta-Endorfina/farmacologia , Animais , Gangliosídeo G(M1)/imunologia , Injeções Intraventriculares , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Naloxona/farmacologia , Linfócitos T/imunologia , beta-Endorfina/administração & dosagemRESUMO
A single intracerebroventricular injection of 100 ng of beta-endorphin altered the course of the central nervous system (CNS) infection of a temperature-sensitive mutant of vesicular stomatitis virus (VSV), tsG31-KS5. When mice were administered beta-endorphin and then 24 h later infected intracerebrally with tsG31-KS5 VSV, 70% of the animals died within 8 days of infection. In comparison, less than 10% of the animals had died after 21 days when infected with tsG31-KS5 VSV alone. When mice were injected with beta-endorphin and tsG31-KS5 VSV simultaneously, or with beta-endorphin 21 days after infection, the more aggressive clinical disease was not observed. Superficially, the more lethal disease induced by beta-endorphin appeared to be a result of a mild hypothermia caused by the neuropeptide. beta-Endorphin, however, did not influence the disease in nude (nu/nu) mice even though their core temperatures were reduced to an extent similar to that of BALB/c (+/+) mice, implicating the involvement of T lymphocytes in the alteration of the course of infection in normal mice.