Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All stress-related inputs are conveyed to the hypothalamus via several brain areas and integrated in the parvocellular division of the paraventricular nucleus (PVN) where corticotropin-releasing hormone (CRH) is synthesized. Arginine vasopressin (AVP) is present in both magnocellular and parvocellular divisions of the PVN, and the latter population of AVP is colocalized with CRH. CRH and AVP are co-secreted in the face of certain stressful stimuli, and synthesis of both peptides is suppressed by glucocorticoid. CRH and AVP stimulate corticotropin (ACTH) secretion synergistically, but the physiological relevance of the dual corticotroph regulation is not understood. Norepinephrine (NE) is a well known neurotransmitter that regulates CRH neurons in the PVN. We explored the mode of action of NE on CRH and AVP gene transcription in the PVN to examine the effect of the neurotransmitter on multiple genes that are responsible for a common physiological function. After NE injection into the PVN of conscious rats, CRH heteronuclear (hn) RNA increased rapidly and markedly in the parvocellular division of the PVN. AVP hnRNA did not change significantly in either the parvocellular or magnocellular division of the PVN after NE injection. The present results show that the transcription of CRH and AVP genes is differentially regulated by NE, indicating the complexity of neurotransmitter regulation of multiple releasing hormone genes in a discrete hypothalamic neuronal population.
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PMID:Differential regulation of corticotropin-releasing hormone and vasopressin gene transcription in the hypothalamus by norepinephrine. 1037 55

The present study investigated the effects of acute administration of cyanamide (a potent inhibitor of aldehyde dehydrogenase used to treat alcoholics), on the hypothalamo-pituitary adrenal (HPA)-axis. Cyanamide resulted in a significant increase in arginine vasopressin mRNA and corticotrophin releasing factor (CRF) mRNA in the parvocellular cells of the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. Plasma corticosterone concentrations were elevated by a range of doses of cyanamide which were maintained in the high dose group at 4 h following administration. These results suggest that cyanamide is able to activate the HPA axis at all levels of the axis. Arginine vasopressin mRNA, in the parvocellular cells of the paraventricular nucleus is an important component of the stress response. Silver grain counting of emulsion dipped slides is commonly used for its evaluation following in-situ hybridization. This method is however, not entirely satisfactory and very time-consuming. We compared this method with a film autoradiographic method, and show that the film autoradiographic method is valid for the determination of arginine vasopressin mRNA in the parvocellular cells of the paraventricular nucleus.
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PMID:Cyanamide-induced activation of the hypothalamo-pituitary-adrenal axis. 1071 21

Enhanced corticosterone release by female compared to male rats under basal and stress conditions is well documented. The demonstration that gonadectomy enhances stress-induced corticosterone secretion in male rats, but reduces such levels in female rats, suggests a causal association between gonadal steroids and corticosterone release. The present study examined the corticosterone profile of sham gonadectomized and gonadectomized female and male rats under basal and stress conditions. An automated sampling system collected blood from each freely moving, unanaesthetized rat every 10 min (i) over a 24-h period; (ii) following noise stress; and (iii) following an immune-mediated stress (lipopolysaccharide, LPS). Plasma was analysed for corticosterone content using radioimmunoassay. Castration resulted in a significant increase in basal corticosterone release compared to the sham-castrated male rats. Pulsar analysis revealed a significant two-fold increase in the number of corticosterone pulses over 24 h. Corticosterone increases in response to noise stress and to LPS injection were enhanced following castration. Conversely, ovariectomy resulted in a two-fold reduction in the number of corticosterone pulses as well as the stress response compared to sham-ovariectomized female rats. Arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH) and glucocorticoid receptor mRNAs in the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary were analysed post-LPS administration by in situ hybridization. Significantly higher values were found for AVP, CRH and POMC mRNAs examined for sham females and castrated males compared to sham males and ovariectomized females. This study confirms previous reports concerning the influence of gonadal factors in regulating HPA axis activity and stress responsiveness. The present results extend these observations to the regulation of the dynamic pattern of corticosterone release under basal conditions and suggests that this alteration in pulsatility is important for the differences in stress responsiveness when comparing males and females.
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PMID:Gonadectomy reverses the sexually diergic patterns of circadian and stress-induced hypothalamic-pituitary-adrenal axis activity in male and female rats. 1518 26

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) secretion from corticotroph cells of the anterior pituitary via activation of the V1b vasopressin receptor, a member of the G protein-coupled receptor (GPCR) family. Recently, we have shown that treatment of ovine anterior pituitary cells with AVP for short periods results in reduced responsiveness to subsequent stimulation with AVP. The aim of this study was to investigate mechanisms involved in this desensitization process. Among the GPCR family, rapid desensitization is commonly mediated by receptor phosphorylation, with resensitization being mediated by internalization and subsequent dephosphorylation of the receptors by protein phosphatases. Since desensitization of V1a vasopressin receptors is mediated by protein kinase C-mediated receptor phosphorylation, we investigated the involvement of this enzyme in desensitization of the ACTH response to AVP. Treatment of perifused ovine anterior pituitary cells with the specific protein kinase C (PKC) activator 1,2-dioctanoyl-sn-glycerol (300 microM) did not induce any reduction in response to a subsequent 5-min stimulation with 100 nM AVP, despite potently stimulating ACTH secretion. Likewise, the results obtained using the PKC inhibitor Ro 31-8220 were not consistent with involvement of PKC in AVP desensitization: 2 microM Ro 31-8220 did not reduce the ability of a 10 nM AVP pretreatment to induce desensitization to a subsequent stimulation with 100 nM AVP. Pharmacologic blockade of receptor internalization by treatment with 0.25 mg/ml concanavalin A significantly impaired the ability of a 15-min pretreatment with 10 nM AVP to induce desensitization, rather than affecting resensitization. Treatment with 10 nM okadaic acid, an inhibitor of protein phosphatase 1 and 2A, had no effect on either resensitization or desensitization. In contrast, inhibition of protein phosphatase 2B (PP2B) with 1 microM FK506 decreased the rate of resensitization: complete recovery from desensitization took 40 min, whereas in controls recovery was complete 20 min after termination of the pretreatment. These results indicate that desensitization of the ACTH response to AVP is not mediated by PKC-catalyzed phosphorylation, suggesting subtype-specific differences in the regulation of V1a and V1b vasopressin receptors. The data demonstrate that desensitization was dependent, at least in part, upon receptor internalization and that resensitization was dependent upon PP2B-mediated receptor dephosphorylation.
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PMID:Mechanisms of desensitization of the adrenocorticotropin response to arginine vasopressin in ovine anterior pituitary cells. 1564 80

Recently, we established that hypothalamo-pituitary-adrenal (HPA) and counterregulatory responses to insulin-induced hypoglycemia were impaired in uncontrolled streptozotocin (STZ)-diabetic (65 mg/kg) rats and insulin treatment restored most of these responses. In the current study, we used phloridzin to determine whether the restoration of blood glucose alone was sufficient to normalize HPA function in diabetes. Normal, diabetic, insulin-treated, and phloridzin-treated diabetic rats were either killed after 8 days or subjected to a hypoglycemic (40 mg/dl) glucose clamp. Basal: Elevated basal ACTH and corticosterone in STZ rats were normalized with insulin but not phloridzin. Increases in hypothalamic corticotrophin-releasing hormone (CRH) and inhibitory hippocampal mineralocorticoid receptor (MR) mRNA with STZ diabetes were not restored with either insulin or phloridzin treatments. Hypoglycemia: In response to hypoglycemia, rises in plasma ACTH and corticosterone were significantly lower in diabetic rats compared with controls. Insulin and phloridzin restored both ACTH and corticosterone responses in diabetic animals. Hypothalamic CRH mRNA and pituitary pro-opiomelanocortin mRNA expression increased following 2 h of hypoglycemia in normal, insulin-treated, and phloridzin-treated diabetic rats but not in untreated diabetic rats. Arginine vasopressin mRNA was unaltered by hypoglycemia in all groups. Interestingly, hypoglycemia decreased hippocampal MR mRNA in control, insulin-, and phloridzin-treated diabetic rats but not uncontrolled diabetic rats, whereas glucocorticoid receptor mRNA was not altered by hypoglycemia. In conclusion, despite elevated basal HPA activity, HPA responses to hypoglycemia were markedly reduced in uncontrolled diabetes. We speculate that defects in the CRH response may be related to a defective MR response. It is intriguing that phloridzin did not restore basal HPA activity but it restored the HPA response to hypoglycemia, suggesting that defects in basal HPA function in diabetes are due to insulin deficiency, but impaired responsiveness to hypoglycemia appears to stem from chronic hyperglycemia.
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PMID:Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal activity in diabetes but it does impair the HPA response to insulin-induced hypoglycemia. 1577 66

Arginine vasopressin (AVP) is a neuropeptide hormone that plays an important role in circulatory and sodium homeostasis, and regulating serum osmolality. Several clinical conditions have been associated with inappropriately elevated levels of AVP including heart failure, cirrhosis of the liver and the syndrome of inappropriate secretion of antidiuretic hormone. Three receptor subtypes that mediate the actions of AVP have been identified (V(1A), V(2) and V(1B)). Activation of V(1A) receptors located in vascular smooth muscle cells and the myocardium results in vasoconstriction and increased afterload and hypertrophy. The V(2) receptors located primarily in the collecting tubules mediate free water absorption. The V(1B) receptors are located in the anterior pituitary and mediate adrenocorticotropin hormone release. The cardiovascular and renal effects of AVP are mediated primarily by V(1A) and V(2) receptors. Antagonism of V(1A) receptors results in vasodilatation and antagonism of V(2) receptors resulting in aquaresis, an electrolyte-sparing water excretion. Several non-peptide AVP antagonists (vasopressin receptor antagonists [VRAs]) also termed 'vaptans' have been developed and are vigorously being studied primarily for treating conditions characterised by hyponatraemia and fluid overload. Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement. It has been shown in clinical trials to correct euvolaemic and hypervolaemic hyponatraemia, and has been approved by the US FDA for the treatment of euvolaemic hyponatraemia as an intravenous infusion. Tolvaptan, a selective V(2)-receptor antagonist, has undergone extensive clinical studies in the treatment of hyponatraemia and heart failure. It has been shown to effectively decrease fluid in volume overloaded patients with heart failure and to correct hyponatraemia. A large outcome study (n = 4133 patients) will define its role in the management of heart failure. Lixivaptan and satavaptan (SR-121463) are other selective V(2)-receptor antagonists being evaluated for the treatment of hyponatraemia. In addition, a potential role for the vaptans in attenuating polyuria in nephrogenic diabetes insipidus and cyst development in polycystic kidney disease is being explored. Ongoing clinical trials should further define the scope of the potential therapeutic role of VRAs.
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PMID:Therapeutic potential of vasopressin receptor antagonists. 1742 3

Arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) have both been implicated in modulating insulin secretion from pancreatic beta-cells. In the present study, we investigated the insulin-secreting activities of AVP and CRH in wild-type and AVP VIb receptor knockout mice. Both neuropeptides stimulated insulin secretion from isolated mouse pancreatic islets. The response of islets to CRH was increased fourfold by concomitant incubation with a subthreshold dose of AVP that alone did not stimulate insulin secretion. Activation of the endogenously expressed M3 receptor by the cholinergic agonist carbachol also potentiated CRH-induced insulin secretion, indicating that the phenomenon may be pathway specific (i.e. Ca2+-phospholipase C) rather than agonist specific. The protein kinase C (PKC) inhibitors Ro-31-8425 and bisindolylmaleimide I attenuated the potentiating effect of AVP on CRH-stimulated insulin secretion and blocked AVP-stimulated insulin secretion. A possible interaction between the PKC and protein kinase A pathways was also investigated. The phorbol ester phorbol myristate acetate (PMA) stimulated insulin secretion, while the addition of both PMA and CRH enhanced insulin secretion over that measured with either PMA or CRH alone. Additionally, no AVP potentiation of CRH-stimulated insulin secretion was observed upon incubation in Ca2+-free Krebs-Ringer buffer. Taken together, the present study suggests a possible synergism between AVP and CRH to release insulin from pancreatic beta-cells that relies at least in part on activation of the PKC signaling pathway and is dependent on extracellular Ca2+. This is the first example of a possible interplay between the AVP and CRH systems outside of the hypothalamic-pituitary-adrenal axis.
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PMID:Vasopressin potentiates corticotropin-releasing hormone-induced insulin release from mouse pancreatic beta-cells. 1843 53

Arginine vasopressin, a hypothalamic peptide hormone, has multiple physiological functions, including body water regulation, control of blood pressure and effects on body temperature, insulin release, corticotropin release, memory and social behaviour. These functions are achieved via at least three specific G-protein-coupled vasopressin receptors. Development of specific vasopressin receptor antagonists in recent years is helping to elucidate the precise actions of vasopressin at each of these receptor types. The complex signalling and messenger processes which take place after receptor stimulation are now more clearly understood. Vasopressin dysregulation can occur in various disease processes, and a better understanding of the mechanisms underlying physiological synthesis, release and regulation of vasopressin will help in the development of therapies to treat these conditions.
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PMID:Physiology and pathophysiology of the vasopressinergic system. 1868 71

Abstract Corticotropin-releasing hormone and arginine vasopressin are known to interact in stimulating secretion of adrenocorticotropin-related peptides from corticotropes. However, the mechanism mediating this interaction is uncertain. Recently, evidence has been provided using a reverse haemolytic plaque assay that in rat pituitary cells, arginine vasopressin potentiates the effects of corticotropin-releasing hormone by increasing the percentage of target cells that secrete adrenocorticotropin. To determine whether a similar mechanism also operates in the sheep corticotrope, which is reportedly more sensitive to arginine vasopressin than that of the rat, a reverse haemolytic plaque assay for beta-endorphin secretion was used to study the response of ovine corticotropes to stimulation by increasing doses of corticotropin-releasing hormone or arginine vasopressin (0.1 nM to 10.0 nM) alone or in combination. In the reverse haemolytic plaque assay, beta-endorphin antiserum at 1:50 and complement at 1:10 were found to be optimal dilutions for plaque formation. A concentration-dependent response curve to corticotropin-releasing hormone was obtained with a significant increase in plaque area from basal to reach maximal levels at 1.0 nM. Arginine vasopressin also stimulated an increase in plaque area, however, plaques formed were significantly smaller than those caused by corticotropin-releasing hormone. Since in the reverse haemolytic plaque assay, plaque area is related to the amount of hormone secreted by the cell, results demonstrate that although corticotropin-releasing hormone and arginine vasopressin both stimulate beta-endorphin secretion from ovine corticotropes, corticotropin-releasing hormone is a more potent secretagogue than arginine vasopressin in that it causes the formation of significantly larger plaques. The addition of arginine vasopressin to low concentrations of corticotropin-releasing hormone caused plaque areas to reach maximal levels at 0.1 nM whereas these levels were only attained at 1.0 nM when corticotropin-releasing hormone was used alone. Therefore, arginine vasopressin interacts with corticotropin-releasing hormone to increase corticotrope responses by increasing their secretory response to corticotropin-releasing hormone. These data are consistent with previous work suggesting that arginine vasopressin increases the expression of corticotropin-releasing hormone receptors on the corticotrope cell surface. However, no significant increase in the percentage of plaque-forming cells was seen with either corticotropin-releasing hormone or arginine vasopressin alone or in combination implying that there was no recruitment of previously non-secreting cells.
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PMID:Reverse haemolytic plaque assay study of corticotropin-releasing hormone and arginine vasopressin interaction in ovine corticotropes. 1921 21

Arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) are released in the brain to regulate behavioral and physiological stress responses. To elucidate the respective roles of these peptides under certain stressors, we examined the effects of intracerebroventricular infusions of either AVP V1a receptor antagonist, [Pmp(1), Tyr (Me)(2)]- Arg(8)-Vasopressin (Pmp, Tyr-AVP) or CRH receptor antagonist, alpha-helical CRF 9-41 (alphahCRF) on stress responses induced by frustrating condition in sheep. Four ovariectomized Corriedale ewes were assigned to the experiment. In a "frustrating" condition (FC), food was withheld for 60 minutes from only the experimental ewe while this ewe was in the presence of the other ewes that were given food. As "non-frustrating" control condition (C), food was withheld for 60 minutes from all ewes, thereby controlling for the nonspecific effects of lack of food. FC induced a significant rise in the plasma cortisol concentration (p < 0.05) and increased the pawing number and rectal temperature compared with that in C (p < 0.1). The effects of either Pmp, Tyr-AVP or alphahCRF on these stress responses were analyzed. The rise in cortisol restored nearly to the control level by infusion of Pmp, Tyr-AVP or alphahCRF. The pawing number restored nearly to the control level by alphahCRF. The hyperthermia restored nearly to the control level by Pmp, Tyr-AVP. These data suggest that both endogenous CRH and AVP might be concerned with inducing physiological and behavioral stress responses to frustrating condition in sheep.
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PMID:Effects of AVP V1a and CRH receptor antagonist on psychological stress responses to frustrating condition in sheep. 1942 Aug 45


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