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)

We readdressed the question of whether or not rat adenohypophyseal vasopressin receptors have a ligand selectivity which is similar to that of the V1 subtype of vasopressin receptors. Vasopressin analogues substituted in positions 7 and 1 were used. By incubating rat anterior pituitary quarters or by perifusing rat isolated anterior pituitary cells, the effect of the vasopressin analogues on the release of beta-endorphin-like or adrenocorticotropin-like immunoreactivity was examined. The replacement of the proline residue in position 7 by sarcosine or N-methyl-alanine did not change the maximum effect reached but increased the EC50 values 20- or 5-fold, respectively, when compared with arginine vasopressin. This decrease in beta-endorphin-releasing activity was no longer observed after additional removal of the alpha-amino group of cysteine in position 1. Since these substitutions are known to drastically reduce vasopressor activity, these data suggest that the beta-endorphin-releasing activity of vasopressin can be dissociated from its V1 receptor activity. Vasopressin analogues substituted in position 7 and with deaminopenicillamine or beta-mercapto-beta,beta-cyclopentamethylenepropionic acid in position 1 were found to be weak antagonists of the beta-endorphin-releasing activity of vasopressin. Since these analogues are potent antagonists at the V1 receptor, these data suggest that the deaminopenicillamine and, more so, the beta-mercapto-beta,beta-cyclopentamethylenepropionic acid residues in position 1 of vasopressin are strong 'binding elements' at the V1 vasopressin receptor but weak 'binding elements' at the adenohypophyseal vasopressin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of rat adenohypophyseal vasopressin receptors with vasopressin analogues substituted at positions 7 and 1: dissimilarity from the V1 vasopressin receptor. 302 2

Vasopressin (CYFQNCPRG-NH(2), AVP) is a semicyclic endogenous peptide, which exerts a variety of biological effects in mammals. The main physiological roles of AVP are the regulation of water balance and the control of blood pressure and adrenocorticotropin hormone (ACTH) secretion, mediated via three different subtypes of vasopressin receptors: V1a, V1b and V2 receptors (V1aR, V1bR and V2R, respectively). They are the members of the class A, G-protein-coupled receptors (GPCRs). AVP also modulates several behavioral and social functions. In this study, the interactions responsible for AVP binding to vasopressin V1a and V2 receptors versus the closely related oxytocin ([I3,L8]AVP, OT) receptor (OTR) have been investigated. Three-dimensional models of the activated receptors were constructed using multiple sequence alignment, followed by homology modeling using the complex of activated rhodopsin with Gt(alpha) C-terminal peptide of transducin MII-Gt(338-350) prototype as a template. AVP was docked into the receptor-G(alpha) systems. The three lowest-energy pairs of receptor-AVP-G(alpha) (two complexes per each receptor) were selected. The 1-ns unconstrained molecular dynamics (MD) of complexes embedded into the fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer was conducted in the AMBER 7.0 force field. Six relaxed receptor-AVP-G(alpha) models were obtained. The residues responsible for AVP binding to vasopressin receptors have been identified and a different mechanism of AVP binding to V2R than to V1aR has been proposed.
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PMID:Analysis of interactions responsible for vasopressin binding to human neurohypophyseal hormone receptors-molecular dynamics study of the activated receptor-vasopressin-G(alpha) systems. 1611

Diabetes, especially type 2, is closely associated with hypothalamo-pituitary-adrenal (HPA) axis regulation. Short-term effects of adrenalectomy (ADX) in type 2 diabetes are well characterized; however, there have been few reports on the long-term effects of ADX in genetically engineered type 2 diabetes and the neuroendocrine system. We performed bilateral ADX in Zucker Lean Control rats (ZLC; ADX-ZLC), Zucker Diabetic Fatty rats (ZDF; ADX-ZDF), and sham control rats to evaluate how the HPA axis would be regulated in long-term corticosterone deficient type 2 diabetic animals. We evaluated arginine vasopressin (AVP), glucocorticoid receptor (GR), and corticotropin-releasing hormone (CRH) expression with immunohistochemistry (IHC), immunofluorescence, real-time PCR, and Western blot analysis in each treatment group 7 weeks post ADX to assess HPA axis regulatory patterns in connection with type 2 diabetes. Additionally, mRNA expression of AVP and CRH receptors (V1aR, V1bR, CRHR1, and CRHR2) was also measured and adrenocorticotropin hormone (ACTH) immunoreactivity was surveyed by IHC to add to data regarding the regulatory mechanism. AVP and CRH protein expression levels increased after ADX in the hypothalamus of diabetic rats based on IHC results; however, we found that the subtypes of each receptor may be regulated differently in ADX groups compared to sham groups. Immunoreactivity of ACTH in the pituitary gland was enhanced in ADX groups and GR expression levels in the hypothalamic paraventricular nuclei (PVN) remained high, as determined by IHC as well as Western blot analysis. Without the negative feedback system of corticosterone, CRH is highly enhanced and may primarily combine with CRHR1 to stimulate negative feedback through ACTH in the pituitary gland in type 2 diabetic rats with long-term ADX. Although the negative feedback signal was not transmitted appropriately following long-term ADX with type 2 diabetes, a high GR protein level was maintained as in type 2 diabetes. The long-termed lack of corticosterone in the blood stream is a very important factor for normal regulation of the HPA axis even in diabetic animals. From the data, we can conclude that the stimulated HPA axis regulation in the developing type 2 diabetic animals following long-term adrenalectomy has remained elevated rather than diminished. Therefore, the current study may provide useful information to better understand patients suffering from both type 2 diabetes and Addison's disease.
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PMID:Regulatory mechanism of hypothalamo-pituitary-adrenal (HPA) axis and neuronal changes after adrenalectomy in type 2 diabetes. 2047 52

The neuroendocrine stress response of vertebrates, particularly mammals, comprises at least two types of neuropeptide containing neurons, corticotropin-releasing hormone (CRH) and vasopressin (VP) neurons, and four receptors [CRH receptor one (CRH-R1) and two (CRH-R2) and VP receptor 1a (V1aR) and 1b (V1bR)]. The avian neuropeptide CRH, a 41-amino acid peptide, has been shown to have the same amino acid sequence as humans while nonapeptide neurohormone arginine-vasotocin (AVT) is regarded as highly conserved having a single amino acid substitution compared to mammalian arginine vasopressin. Similar to mammals, birds have two receptor subtypes (CRH-R1 and CRH-R2) for CRH, however, four vasotocin receptors have been identified. Less is known about the functions of the four avian vasotocin receptors compared to homologous ones found in mammals and other vertebrate classes. Recently, chicken vasotocin receptor two (VT2R) and four (VT4R) have been characterized utilizing immunocytochemistry and an imposed stress test. The purpose of this review is to present evidence that the VT2R and VT4R are involved in the avian stress response and that the cephalic lobe of the anterior pituitary appears specialized for this function as it contains the major population of corticotropes and necessary neuroendocrine receptors to respond to stressors impacting avian species.
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PMID:Neuroendocrine regulation of stress in birds with an emphasis on vasotocin receptors (VTRs). 2350 Jun 73

Vasotocin 1a and 1b receptors (V1aR and V1bR) have been shown to play important roles in the neuroendocrine regulation of stress responses via the anterior pituitary (AP) of birds. To identify effective subtype-specific antagonists for the chicken V1aR (cV1aR) and cV1bR, potential antagonists to the mammalian V1R were screened against the cV1aR and cV1bR 3D structural models by molecular docking analysis with determination of binding pocket/amino acid residues involved in the interaction. The antagonistic effects of the selected ligands were examined by measuring pro-opiomelanocortin (POMC) heteronuclear RNA (hnPOMC) levels following the in vitro stress administration to primary chicken AP cells. Results of in silico analysis showed that the Manning compound and several other antagonists were bound to cV1bR with higher affinity than the natural agonist, arginine vasotocin (AVT). Similarities and differences in the antagonist-receptor binding interface with receptors were characterized for each ligand. Non-peptide mammalian V1bR antagonists, SSR-149415 and L-368899, were shown to be effective and had an additive effect in blocking POMC hnRNA expression in pituitary cell culture studies. SR-49059 antagonized the effect(s) of AVT/CRH on the downregulation of the cV1aR and the upregulation of the cCRH-R2 expression but not the cV1bR and cCRH-R1. The Manning compound antagonized the downregulation of cV1aR, cV1bR and cCRH-R1 and the upregulation of cCRH-R2 expression. The specificity of antagonists apparently resulted from unique differences in the interacting residues and their binding affinities. Collectively, these results provide valuable leads for future development of novel compounds capable of blocking or attenuating the AP stress response of avian species and perhaps other non-mammalian vertebrates as well.
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PMID:Identification of avian vasotocin receptor subtype-specific antagonists involved in the stress response of the chicken, Gallus gallus. 2965 87