Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following a brief review of the preferred three-dimensional structured proposed for oxytocin in dimethylsulfoxide and in aqueous medium, the "cooperative model" for the biologically active conformation of oxytocin is discussed. An approach to conformation-activity analysis is described. The importance of determining the peptide backbone conformation and the functional contribution of peptide backbone and amino acid side chains to hormone receptor interactions are analyzed. Sites are proposed that are thought to be involved in the binding process of oxytocin to the smooth muscle receptor in rat uterus, as well as sites that are thought to be responsible for receptor activation.
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PMID:Indentification of sites in oxytocin involved in uterine receptor recognition and activation. 19 3

The oxytocin analogue, 2-nitro-5-azidobenzoylglycyloxytocin (NAB-Gly-oxytocin), has been synthesized and purified. The analogue is a full agonist for the stimulation of osmotic water flow in the toad urinary bladder (one-half maximal activity at 3.2 X 10(-6)M). It also enhances [14C]urea permeability in this tissue. Repetitive photolysis in the presence of NAB-Gly-oxytocin (8 X 10(-6)M) results in a progressive permanent inhibition of oxytocin stimulated urea permeability but does not alter hormone induced 3H2O movement. The inhibition is dependent on the photogeneration of the aryl nitrene intermediate and is relieved by protecting the hormone receptor with excess oxytocin (10(-6)M) during the photolysis. These results suggest that the photodependent permanent inhibition of the response to oxytocin in the toad bladder is due to covalent incorporation of the photoaffinity label, NAB-Gly-oxytocin, into the hormone receptor.
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PMID:Synthesis and characterization of 2-nitro-5-aziodobenzoylglycyloxytocin, an oxytocin photoaffinity label. 20 76

A study to determine the feasibility of photoaffinity labeling the antidiuretic hormone receptor in the toad urinary bladder has been carried out. Two photoactivated derivatives of oxytocin have been synthesized, purified, and characterized chemically and biologically. Photolysis of the toad bladder in the presence of one of these derivatives, 2-nitro-5-azidobenzoylglycyloxytocin, produces a permanent inhibition of the response to native oxytocin. This inhibition can be relieved by protecting the hormone receptor with excess oxytocin during the photolysis. These results suggest that the photolysis-dependent inhibition of the response to native hormone is due to covalent incorporation of the photoaffinity label into the hormone receptor.
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PMID:Photoaffinity labeling of the antidiuretic hormone receptor. 21 72

The neurohypophyseal neuropeptides (Arg8)-vasopressin (AVP) and [pGlu4,Cyt6]AVP-(4-8) (where pGlu is pyroglutamic acid and Cyt is cystine) facilitate the retention of one-trial-learning passive avoidance behavior in rats when administered into the cerebral ventricle immediately after the learning trial. The fragment [pGlu4,Cyt6]AVP-(4-8) was considerably more effective than AVP. Oxytocin (OXT) and [pGlu4,Cyt6]OXT-(4-8) have the opposite effect and attenuate passive avoidance behavior also when administered into the cerebral ventricle after the learning trial. Again the fragment was more active than the parent molecule. The ancient arginine-containing neurohypophyseal hormone vasotocin in "high" doses (10ng) had a vasopressin-like effect and in "low" doses (0.1 ng) had an OXT-like effect on passive avoidance behavior. Because both vasopressinergic (V1) and oxytocinergic receptors have been demonstrated in the central nervous system, we asked whether specific antagonists of the V1, V2, and OXT receptor could antagonize the effects of these neuropeptides on passive avoidance behavior. The three antagonists were approximately equally active in blocking the effect of vasopressin, whereas the fragment [pGlu4]AVP-(4-8) and the high dose of vasotocin were more readily blocked by the OXT antagonist. The attenuating effect of OXT, the fragment [pGlu4,Cyt6]OXT-(4-8), and the low dose of vasotocin was markedly reduced by the OXT antagonist. This effect could also be reduced by pretreatment with the V1 antagonist but not with the V2 antagonist. These results suggest the existence of a separate neurohypophyseal hormone receptor complex in the brain affecting memory processes that differs from the peripheral V1, V2, and OXT receptor.
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PMID:Interactive effects of neurohypophyseal neuropeptides with receptor antagonists on passive avoidance behavior: mediation by a cerebral neurohypophyseal hormone receptor? 184 26

Vasopressin receptors were demonstrated on human peripheral blood mononuclear cells (PBMC) by using the radioiodinated analog of d(CH2)5[Tyr(Me2)Thr4Tyr-NH2(9)]OVT (OTA). Binding of this ligand was time-dependent, specific, and saturable. Scatchard analysis of [125I]-OTA binding at equilibrium revealed a dissociation constant of 0.47 +/- 0.17 nM. A considerable sex difference in binding capacity was observed. PBMC from female donors expressed an approximately sevenfold higher receptor density than PBMC from male donors, while no change of Kd was apparent. Throughout the menstrual cycle the maximal binding capacity was relatively constant. Competition studies with vasopressin and oxytocin analogs showed that this putative receptor site on PBMC is comparable in receptor specificity to the human V1 receptor on myometrial tissue and blood platelets, but slightly different from the rat neurohypophyseal hormone receptor classes. Our findings provide further evidence of a remarkable species and sex difference of vasopressin and oxytocin receptors, regarding their ligand selective binding properties. The presence of the putative arginine-vasopressin receptors on PBMC may provide a molecular basis for several arginine-vasopressin induced effects on the chemistry and function of circulating mononuclear cells.
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PMID:Vasopressin receptor capacity of human blood peripheral mononuclear cells is sex dependent. 213 99

1. We have developed a plasma membrane preparation from the mucosal epithelium of rabbit gallbladder and have characterized the hormonal sensitivity of adenylate cyclase in this preparation. 2. Basal activity is low and is stimulated by GTP and GppNHp. Hormonal stimulation is largely dependent on exogenous guanine nucleotide. 3. Several prostaglandins (E1 approximately E2 greater than A1 greater than B1), vasoactive intestinal peptide and the beta-adrenergic agonist, isoproterenol, stimulate mucosal adenylate cyclase activity; a variety of peptides and neurotransmitters (secretin, cholecystokinin, arg-vasopressin, oxytocin, histamine, dopamine and serotonin) are without effect. 4. The data support the hypothesis that the inhibitory effect of prostaglandins, vasoactive intestinal peptide, and isoproterenol on gallbladder fluid absorption in certain species may be mediated by cyclic AMP. 5. The membrane preparation should be useful in further characterizing hormone receptor-transducer interactions of the gallbladder mucosal epithelium.
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PMID:Characterization of hormone-sensitive adenylate cyclase in rabbit gallbladder mucosa. 254 33

The promoter regions of the rat corticotropin-releasing factor (CRF), oxytocin (OT), and vasopressin (AVP) genes contain sequences similar to the cis-acting response element identified for NGFI-B, an immediate-early gene structurally related to the steroid hormone receptor superfamily. Combined immuno- and hybridization histochemical approaches were used to determine whether challenges that influence the synthesis and secretion of CRF, OT, and/or AVP result in altered expression in neurosecretory neurons of NGFI-B and another immediate-early gene, c-fos, which is widely used as a marker for functionally activated neurons. NGFI-B mRNA was found to be expressed at constitutively high levels in the telencephalon, but not in the endocrine hypothalamus, of unperturbed controls; basal levels of c-fos expression were uniformly low throughout the CNS. NGFI-B and c-fos mRNAs, and Fos protein, were induced with a similar time course and in similar neuroendocrine cell types in response to acute hypotensive hemorrhage (15% reduction in blood volume), intravenous injection of interleukin-1 beta (IL-1 beta; 1.87 micrograms/kg), chronic salt loading (7 d maintenance on 2% saline), and acute bilateral adrenalectomy. c-fos mRNA and Fos protein were readily demonstrable in afferent pathways that have been implicated as mediating the neuroendocrine responses in the three stress paradigms; these include medullary catecholaminergic cell groups in response to IL-1 beta and hemorrhage, and cell groups lining the lamina terminalis in response to salt loading. Challenge-specific induction of NGFI-B expression was detectable in these extrahypothalamic cell groups, though with a lesser sensitivity than that required to reveal NGFI-B induction in the hypothalamus, or c-fos expression in these related afferents. These results establish NGFI-B as a useful adjunct to c-fos, for revealing synaptic and/or transcriptional activation in the magno- and parvocellular neurosecretory systems. Differences in the sensitivity of the two markers in revealing functionally related activation in extrahypothalamic regions speak to general issues concerning the use of immediate-early genes in mapping functional circuitry in the CNS.
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PMID:A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry. 825 63

The dissociation course of the hormone receptor complexes of rat myometrial oxytocin receptors was studied. The dissociation course was biphasic with a major component displaying an almost irreversible binding character (time constant 0.003 min-1). This irreversibility was independent of hormonal status of the myometrium as well as the type of divalent cation present in the medium, and was not caused by endocytosis of the receptor. However, as addition of EDTA caused an immediate dissociation of all receptor binding, the irreversibility must be of a non-covalent character. It is suggested that new analysis methods for receptor kinetics including the possibility of partly irreversible binding mechanisms should be considered.
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PMID:The nature of receptor binding of oxytocin in myometrial tissue. 838 57

We analysed the effects of specific neurohypophysial analogues for pharmacological characterization of the type of vasotocin receptor involved in the control of the adrenocorticotrophin hormone (ACTH) release from the perifused pituitary in the rainbow trout, Oncorhynchus mykiss. Mammalian corticotrophin releasing factor (CRF) and teleostean neurohypophysial peptides (arginine vasotocin (AVT) and isotocin (IT)) stimulated ACTH release. Analysis of concentrations giving half-maximal effects (D50) showed that these peptides affected ACTH release in the following order of potency: CRF (8 x 10(-13) M) > AVT (2 x 10(-10) M) > IT (10(-7) M). Maximal responses (Dmax) were obtained for hormonal concentrations of 10(-10) M, 10(-8) M and 10(-6) M respectively. This suggests that AVT and IT have different roles in the control of ACTH release. The values obtained for AVT and IT were in agreement with the circulating levels we previously found for these peptides. Specific V1 or V2 agonists or antagonists (with reference to vasopressin in mammals) were used to define the specificity of the neurohypophysial peptide receptor involved in this stimulation. The V1 agonist, [Phe2, Orn8]-oxytocin, stimulated ACTH release while the V2 agonist, [deamino1, Val4, D-Arg8]-vasopressin, had no such effect. Maximal and half-maximal responses were obtained in the presence of the V1 agonist with 10(-7) M and 7 x 10(-9) M respectively, and were in the range of values obtained with natural peptides. The V1 antagonist, [d(CH2)5(1), O-Me-Tyr2, Arg8]-vasopressin, and the V2 antagonist, [d(CH2)5(1), D-Ile2, Ile4, Arg8, Ala9]-vasopressin, maximally reversed the 10(-9) M AVT-stimulated ACTH release by 60% and 25% respectively, for a 5 x 10(-10) M concentration of the analogues and a D50 approximately 2 x 10(-11) M. These results demonstrated the presence of only one V1-type receptor in fish pituitary, with some of the structural and functional peculiarities typically displayed by the mammalian V1a-type receptor, but distinct from it. In this sense, the fish pituitary vasotocin receptor may represent a novel type of neurohypophysial hormone receptor, more closely related to the mammalian V1b-type.
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PMID:A V1-type receptor for mediating the neurohypophysial hormone-induced ACTH release in trout pituitary. 867 42

The neurohypophyseal nonapeptide oxytocin (OT) is the main hormone responsible for the initiation of labor; uterus contraction can be enhanced by application of oxytocin or suppressed by oxytocin antagonists. By transfer of domains from the G protein-coupled OT receptor into the related V2 vasopressin receptor, chimeric "gain in function" V2/OT receptors were produced that were able to bind either OT receptor agonists or a competitive peptide antagonist with high affinity. The binding site for the OT antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9]vasotocin was found to be formed by transmembrane helices 1, 2, and 7 with a major contribution to binding affinity by the upper part of helix 7. These transmembrane receptor regions could be excluded from participating in OT binding. For agonist binding and selectivity the first three extracellular receptor domains were most important. The interaction of the N-terminal domain and of the first extracellular loop of the OT receptor with the linear C-terminal tripeptidic part of oxytocin was demonstrated. Furthermore, the second extracellular loop of the OT receptor could be identified to interact with the cyclic hormone part. These three domains contribute to OT binding by synergistic interaction with oxytocin but not with the competitive antagonist. Our results provide evidence for the existence of separate domains and different conformations of a peptide hormone receptor involved in binding and selectivity for agonists and peptide antagonists.
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PMID:Separate agonist and peptide antagonist binding sites of the oxytocin receptor defined by their transfer into the V2 vasopressin receptor. 894 Jan 77


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