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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study the interactions of oxytocin with the transmembrane region of the oxytocin receptor were modelled in order to explain the selective binding of oxytocin and vasopressin. Three sites of interaction in the receptors were identified by sequence comparison and model building. Both receptors share one site, which is formed by glutamine residues. This site binds the Asn-5 common to both hormones. The second site is a specific hydrophobic pocket formed by isoleucine and phenylalanine residues. A third interaction is between a conserved tyrosine and the glutamine of vasopressin and oxytocin. The model suggests that one receptor residue in the transmembrane region is responsible for the specificity of the receptors. The model may be used in the rational design of non peptide analogues for the hormones.
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PMID:Modelling the peptide receptor interaction: selectivity of the oxytocin receptor. 806 Mar 40

Vasopressin (AVP), the antidiuretic hormone, is a cyclic nonapeptide that acts through binding to G protein-coupled specific membrane receptors pharmacologically divided into three subtypes (V1a, V1b, and V2) linked to distinct second messengers. Within the family of human AVP receptors, the V2 AVP receptor has been cloned, but the structure of the human V1a and V1b AVP receptors remains unknown. We report here the structure and functional expression of a human V1a AVP receptor complementary DNA isolated from human liver cDNA libraries. Cloning and sequencing of a full-length clone isolated a 1472-nucleotide sequence encoding a 418-amino acid polypeptide with seven putative transmembrane domains typical of G protein-coupled receptors. Amino acid sequence identity with the rat liver V1a AVP receptor, the human and rat V2 AVP receptors, and the human oxytocin receptor was 72, 36, 37, and 45%, respectively. Functional characterization of the cloned receptor was done by transient expression in COS-7 cells and stable expression in Chinese hamster ovary cells. Localization of the expressed receptor at the cellular surface was illustrated by using the fluorescent linear analog phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2 coupled to fluorescein-avidin by dodecabiotin. Competition binding experiments with phenylacetyl-D-Tyr(Et)-Phe-Val-Asn-Lys-Pro-[125I]Tyr-NH2 and AVP analogs revealed high affinity specific binding sites of the V1a subtype. Saturation binding experiments with [3H]AVP confirmed the presence of a single class of high affinity binding sites. Measurement of AVP-induced inositol phosphate production and calcium mobilization confirmed that the expressed V1a AVP receptor is coupled to phospholipase C via a pertussis toxin-insensitive pathway. Thus, the human V1a AVP receptor belongs to the superfamily of seven-transmembrane segment receptors with a significant sequence identity with the other members of the AVP-oxytocin family of receptors.
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PMID:Molecular cloning, sequencing, and functional expression of a cDNA encoding the human V1a vasopressin receptor. 810 69

The neurohypophyseal peptide hormone oxytocin functions as a neuropeptide in several brain areas in addition to its role as a posterior pituitary hormone. Several studies have determined significant differences in patterns of oxytocin receptor binding in the brains of two closely related species of vole. One of the defining features of these two species is remarkably different reproductive behavior strategies. The prairie vole forms long-term monogamous relationships; the montane vole is polygamous. One potential measure of the formation of a pair bond in prairie voles is the development of intense aggressive behavior directed at male conspecifics following a mating bout. Oxytocin had little effect on aggressive behavior when administered before mating but had profound effects on the aggression of male prairie voles when administered after mating. Oxytocin had relatively modest effects on the behavior of montane voles, and neither the behavior nor the peptide effects were affected by mating experience. The data indicate that differences in peptide binding in these two species of vole may be functionally related to difference in social behavior.
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PMID:Oxytocin and complex social behavior: species comparisons. 812 69

We have previously characterized specific oxytocin receptors in the rat anterior pituitary gland, using a highly selective oxytocin receptor antagonist as radioligand. The aim of the present study was to examine whether occupation of these receptors by oxytocin produces a stimulation of prolactin release and a rise in the accumulation of total inositol phosphates in the rat adenohypophysis. Anterior pituitary cells harvested from randomly cycling and diethylstilboestrol (100 micrograms s.c.)-treated rats were perifused with Dulbecco's minimal essential medium at a rate of 0.3 ml/min. Oxytocin and the specific oxytocin agonist [Thr4-Gly7]-oxytocin (TG-OT) both stimulated a significant prolactin release at concentrations of 10(-6) and 10(-7) M. Oestrogen treatment did not affect the response to oxytocin, indicating that there is no straightforward correlation between receptor number and prolactin secretory response in the rat pituitary gland. The involvement of phosphoinositide hydrolysis was investigated in dispersed anterior pituitary cells and uterine tissue from randomly cycling rats. Oxytocin and arginine-vasopressin stimulated a significant (P < 0.05) and dose-related increase in total inositol phosphates, vasopressin being more potent. The specific oxytocin agonist TG-OT had no effect on total inositol phosphate production in pituitary cells, but when tested in uterine tissue it significantly (P < 0.05) stimulated the accumulation of total inositol phosphate at all concentrations tested (10(-5) to 10(-9) M). In conclusion, the data show that oxytocin has prolactin-releasing activity, acting on specific receptors in the anterior pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific oxytocin agonist stimulates prolactin release but has no effect on inositol phosphate accumulation in isolated rat anterior pituitary cells. 838 9

In renal collecting duct epithelial cells, arginine vasopressin (AVP) at greater than nanomolar concentrations has been reported to transiently increase intracellular free calcium ([Ca2+]i) in a manner consistent with activation of the phosphoinositide pathway. To investigate whether any of the known neurohypophysial hormone subtypes are involved, we measured [Ca2+]i in microdissected rat terminal inner medullary collecting duct (IMCD) using fura-2. To allow quantitative comparisons of the response under different conditions, we determined the areas under the response curves (in nM.min) over 1.5 min using numerical integration. AVP, the V1b-receptor agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin, the V2-receptor agonist 1-desamino-8-D-arginine vasopressin, oxytocin, and the selective oxytocin-receptor agonist [Thr4,Gly7]oxytocin (TG-OXT), each at 10 nM, significantly increased [Ca2+]i (69.52 +/- 10.25, 27.0 +/- 11.7, 24.33 +/- 5.83, 14.75 +/- 2.81, and 14.57 +/- 3.50 nM.min, respectively). In contrast, a V1a-selective agonist ([Phe2,Ile3,Orn8]vasopressin) did not increase [Ca2+]i (0.43 +/- 2.36 nM.min). In desensitization studies, challenge with 10 nM AVP or TG-OXT completely prevented a rise in [Ca2+]i in response to immediate rechallenge with the same agent, but not the other, demonstrating homologous desensitization. The lack of cross-desensitization implies that at least two receptors are present that can trigger a rise in [Ca2+]i in response to neurohypophysial hormones. Antagonists for oxytocin ([des-glycinamide9,d(CH2)5(1),O-Me-Tyr2,Thr4,Orn8]vaso tocin), V2 ([d(CH2)5(1),D-Ile2,Ile4,Arg8]vasopressin), and V1a ([d(CH2)5(1),O-Me-Tyr2,Arg8]vasopressin) receptors partially inhibited the [Ca2+]i response induced by 10 nM AVP (89.5, 81.6, and 51.4% inhibition, respectively). These data are consistent with the view that both an oxytocin receptor and a vasopressin receptor are coupled to a [Ca2+]i mobilization response in rat terminal IMCD. This vasopressin receptor is distinct from both the V1a receptor and the V2 receptor and may be either the V1b receptor or a novel vasopressin receptor subtype.
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PMID:Vasopressin and oxytocin receptors coupled to Ca2+ mobilization in rat inner medullary collecting duct. 839 22

[Arg8]vasopressin and oxytocin are the two main members of the neurohypophysial hormone family found to be present in nearly all mammals. [Lys8]vasopressin ([Lys8]VP) has been identified as the antidiuretic hormone in pig and some marsupial families. The porcine-derived kidney epithelial cell line, LLC-PK1, expresses both [Lys8]VP receptors coupled to the activation of adenylate cyclase (V2 receptors) and oxytocin receptors. Here we report the molecular cloning of the V2 [Lys8]VP receptor and the oxytocin receptor from LLC-PK1 cells. The cloned V2 [Lys8]VP receptor differs from human and rat V2 [Arg8] receptors mainly in its N-terminal region, in residues located in the extracellular loops and in intracellular phosphorylation sites. When expressed in COS7 cells, the V2 [Lys8]VP receptor exhibits the relative order of ligand affinity [Lys8]VP = [Arg8]VP >> 1-deamino[D-Arg8]VP > or = oxytocin and adenylate-cyclase stimulation, expected for the porcine V2 [Lys8]VP receptor but different from V2 [Arg8]VP receptors. Adenylate-cyclase activation by [Lys8]VP was inhibited in COS7 cells by a V2 antagonist. The cloned oxytocin receptor exhibits in COS7 cells a ligand specificity typical of mammalian oxytocin receptors. mRNA-distribution analysis revealed a single 5.5-kb transcript in the uterus from pregnant guinea pig.
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PMID:Molecular cloning and functional characterization of V2 [8-lysine] vasopressin and oxytocin receptors from a pig kidney cell line. 839 86

In order to understand the molecular mechanisms that underlie the co-evolution of related yet functionally distinct peptide-receptor pairs, we study receptors for the vasopressin-related peptide Lys-conopressin in the mollusc Lymnaea stagnalis. In addition to a previously cloned Lys-conopressin receptor (LSCPR1), we have now identified a novel Lys-conopressin receptor subtype, named LSCPR2. The two receptors have a differential distribution in the reproductive organs and the brain, which suggests that they are involved in the control of distinct aspects of reproduction and mediate transmitter-like and/or modulatory effects of Lys-conopressin on different types of central neurons. In contrast to LSCPR1, LSCPR2 is maximally activated by both Lys-conopressin and Ile-conopressin, an oxytocin-like synthetic analog of Lys-conopressin. Together with a study of the phylogenetic relationships of Lys-conopressin receptors and their vertebrate counterparts, these data suggest that LSCPR2 represents an ancestral receptor to the vasopressin/oxytocin receptor family in the vertebrates. Based on our findings, we provide a theory of the molecular co-evolution of the functionally distinct ligand-receptor pairs of the vasopressin/oxytocin superfamily of bioactive peptides.
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PMID:Co-evolution of ligand-receptor pairs in the vasopressin/oxytocin superfamily of bioactive peptides. 863 71

1. The intracellular Ca2+ concentration ([Ca2+]1) was monitored in single magnocellular neurones freshly isolated from rat supraoptic nucleus. Application of 100 nM vasopressin increased [Ca2+]1. Two types of [Ca2+]1 responses were observed: (i) a transient response, displayed by 86% of the vasopressin-sensitive neurones, and (ii) a sustained response displayed by 14% of the vasopressin-sensitive neurones. 2. Among responding neurones, 52% were vasopressin sensitive, 44% were oxytocin sensitive and 4% were sensitive to both peptides. 3. Responses to vasopressin were dose dependent, showed a progressive desensitization after successive applications, were specifically blocked by the V1a vasopressin receptor antagonist, SR 49059, and were unaffected by the oxytocin receptor antagonist, d(CH2)5OVT. 4. Vasopressin responses were completely suppressed by the removal of external Ca2+. 5. The intracellular Ca2+ mobilizers, caffeine and tBuBHQ, did not affect resting or vasopressin-induced [Ca2+]1 changes. Thapsigargin (200 nM) on its own evoked an increase in [Ca2+]1, and reduced the [Ca2+]1 increase evoked by vasopressin by 52%, suggesting that thapsigargin-sensitive Ca2+ stores are partially involved in the vasopressin response. 6. Immunocytochemical identification revealed that vasopressin-responding neurones synthesize vasopressin whereas oxytocin-responding neurones synthesize oxytocin. 7. In conclusion, vasopressin- (partially external Ca2+ dependent) and oxytocin (totally external Ca2+ independent)-induced [Ca2+]1 changes are mediated by specific receptors. In addition, vasopressin and oxytocin neurones are specifically autoregulated by their own peptides.
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PMID:Vasopressin-induced intracellular Ca2+ increase in isolated rat supraoptic cells. 868 70

The present study aims at delineating residues in the vasopressin/oxytocin receptor family responsible for the high affinity binding of the hormone. Therefore, we have constructed a computer-generated 3 dimensional model of the rat V1a vasopressin receptor subtype which allowed us to propose residues likely to be involved in agonist binding. Among these residues, several are highly conserved in the receptor family. They were selected for site-directed mutagenesis on the basis of putative direct interaction with bound ligands. The present model and experimental results led us to conclude that the hormone is docked in a pocket completely buried in the transmembrane core of the receptor. Large polar residues, such as glutamine and lysine, located in transmembrane regions 2,3,4 and 6 are involved in the binding of the neurohypophysial hormone. Since all the mutated residues are highly conserved in AVP and OT receptors, we propose that the agonist binding site is similar in all members of the receptor family; only minor changes were found in antagonist potencies, suggesting that agonist and antagonist binding sites do not completely overlap.
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PMID:Identification of agonist binding sites of vasopressin and oxytocin receptors. 871 80

Vasopressin (AVP) and oxytocin (OT) are two nonapeptides differing at position 3, in the cyclic part of the peptide, and at position 8, in the C-terminal tripeptide. In this study, we have evaluated the interactions between these two positions of the hormones and the oxytocin receptor (OTR), the V1a and the V2 vasopressin receptors. The contribution of these two positions to receptor selectivity was analyzed by using several peptide analogues bearing substitutions at either position 3 or 8. The putative interactions between receptor residues and hormone residues at position 3 and 8 were then deduced by using a three dimensional model of the neurohypophysial hormones docked into their respective receptors. On the basis of this model, we found that the lateral chain of residue 8 might interact with residues located in the first extracellular loop. By using site-directed mutagenesis on the cloned receptors, we identified a non-conserved residue in the first extracellular loop that interacts with the lateral chain of residue 8 in the hormone. We demonstrated that this interaction is crucial for receptor selectivity to the different agonists.
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PMID:Molecular basis for agonist selectivity in the vasopressin/oxytocin receptor family. 871 82


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