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)

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 molecular cloning and characterization of receptors for [Arg8] vasopressin and oxytocin were recently accomplished. These receptors form a subfamily among the large number of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors with seven transmembrane domains. The molecular cloning of the human V2 receptor was rapidly followed by the identification of mutations in the V2 receptor gene segregating with the clinical phenotype in families with X-linked nephrogenic diabetes insipidus. These naturally occurring mutations will be useful to identify critical functional regions of the vasopressin V2 receptor. Carrier detection and early diagnosis of affected male infants are available and can avert the physical and mental retardation that are the consequences of episodes of dehydration. Together with the recent cloning of the vasopressin-regulated water channels in the apical membrane of the collecting tubule, these developments will enable direct investigation of the mammalian concentrating mechanism.
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PMID:Molecular and cellular biology of vasopressin and oxytocin receptors and action in the kidney. 785 Apr 11

Vasopressin immunostaining in the lateral septum of the European hamster (Cricetus cricetus L.) disappears in autumn, at the time of the first appearance of hypothermic periods characteristic to hibernation. Previous results have shown that chronic administration of vasopressin in the lateral septum during winter prevents the expression of hypothermic periods, suggesting a role for this peptide in hibernation. It is now observed that acute infusion of vasopressin, and in 50% of the cases, of a specific vasopressin V1 receptor agonist, during a hypothermic period results in an immediate termination of hypothermia. Infusion of oxytocin or a vasopressin V2 receptor agonist were without effect. The results indicate that the seasonal variation in central vasopressin activity, possibly through an interaction with V1 receptors, may play an important role in the expression of hibernation in the European hamster.
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PMID:Induction of arousal in hibernating European hamsters (Cricetus cricetus L.) by vasopressin infusion in the lateral septum. 813 Oct 59

The increase in blood clotting factor VIII (antihaemophilic factor, F-VIII) and fibrinolytic activity induced by the administration of neurohypophyseal hormone analogues, was assayed in sheep. Peptides with high selectivity for vasopressin V1, V2 or myometrial oxytocin receptors in the dose range of 0.1-10 micrograms/kg body weight were investigated. The main conclusions are as follows. The time-course of the F-VIII plasma levels following the administration of the peptides was biphasic, with one surge at about 20 min, a rebound phase, and another increase with the maximum at 60-90 min. The time-course of the fibrinolytic response, expressed as biological activity of plasminogen activator in the plasma euglobulin fraction, displayed a single maximum within 60 min. The baseline responses were reached within 90-120 min. Responses were expressed as integrals of the time-concentration curves in a predetermined time range (90-120 min). F-VIII and plasminogen activator enhancing effects seemed to be tightly linked to the specific vasopressin V2 receptor activities. [Val4,D-Arg8]Vasopressin displayed higher plasminogen activator activities than the standard substance, deamino[D-Arg8]vasopressin. The vasotocin analogue [Phe2,Orn8]oxytocin, a specific vasopressin V1 receptor agonist, also displayed high antihaemophilic and fibrinolytic potencies, expressed in terms of ED50 values, but did not reach the same maximal response as vasopressin V2 receptor agonists. Oxytocin and its highly selective uterotonic analogue, [Thr4,Gly7]oxytocin, displayed low antihaemophilic, and virtually no plasminogen activating potencies. Surprisingly, vasopressin V2 and V1V2 receptor antagonists studied in our experiments showed both enhanced F-VIII and fibrinolytic responses. Dose-response curves frequently displayed a decrease of the F-VIII, and sometimes also decreased fibrinolytic responses, at higher peptide doses. Strong decreases of the packed cell volume (haematocrit) and somewhat lower decreases of the total plasma protein concentration were observed shortly after administration of the peptides.
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PMID:Effects of neurohypophyseal hormone analogues on blood clotting factor VIII and fibrinolytic activity in sheep. 912 40

The role of central vasopressin V1 receptors in grooming behavior induced by vasopressin and oxytocin was studied in male rats of the Wistar strain. The intracerebroventricular (ICV) injection of vasopressin (3 micrograms/5 microliters) induced hypothermia and enhanced novelty-induced grooming behavior. Enhanced grooming but not hypothermia was also induced by ICV injection of oxytocin (3 micrograms/5 microliters). The central administration of a selective vasopressin V1 receptor antagonist prevented the stimulating action of vasopressin on novelty-induced grooming and its hypothermic effect. The ICV injection of a selective vasopressin V2 receptor antagonist failed to affect vasopressin-induced grooming and hypothermic effect. An increase in core temperature was observed in oxytocin-injected animals pretreated with the vasopressin V1 receptor antagonist. Furthermore, pretreatment with the antagonist did not affect grooming induced by oxytocin. These results suggest that enhancement of grooming behavior and influence on thermoregulation are differently regulated by central receptors for vasopressin and oxytocin.
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PMID:The block of central vasopressin V1 but not V2 receptors suppresses grooming behavior and hypothermia induced by intracerebroventricular vasopressin in male rats. 939 41

The effect of vasopressin and oxytocin on the contractile activity of preparations isolated from the feline gastric corpus wall was investigated. Vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M), but not oxytocin, evoked concentration-dependent tonic contractions only of longitudinal muscle strips. At the same time, vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M) potentiated the magnitude of amplitudes, but not the frequency, of spontaneous contractions. Both the vasopressin V1 receptor antagonist d(CH2)5-(Me)2-Tyr-AVP and the predominantly vasopressin V2 receptor antagonist d(CH2)5, D-Ile2, Ile4-AVP, the non-selective muscarinic receptor antagonist, atropine, the predominantly selective muscarinic M1 receptor antagonist, pirenzepine, the predominantly selective muscarinic M2 antagonist, methoctramine, the predominantly selective muscarinic M3 receptor antagonist, para-fluoro-hexahydro-siladifenidol, and the calcium channel blocker, nifedipine, but not the ganglion blocking agent, mecamylamine, depressed or blocked the tonic contractions induced by vasopressin. Among the antagonists, only atropine and nifedipine inhibited the spontaneous contractions. On the other hand, the anticholinesterase, physostigmine, potentiated both the vasopressin-induced tonic and spontaneous contractions. With regard to the receptors, the vasopressin-induced tonic contractions are mediated at least in part through vasopressin V1 and V2 receptors, non-selective muscarinic and selective muscarinic M1, M2 and M3 receptors. The increase in amplitudes of spontaneous contractions is mediated only via-nonselective muscarinic receptors. Vasopressin receptors appear to be located mostly pre-synaptically, although the direct effect of vasopressin on post-synaptic receptors cannot be excluded. The pA2 values suggests rather V1a than V1b vasopressin receptor subtype involvement in tonic contractions vasopressin had produced. The tonic as well as spontaneous contractions are calcium-dependent. In addition, these results point to the existence of non-selective muscarinic receptors, which participate in the regulation of both tonic and spontaneous contractions, while muscarinic M1, M2 and M3 receptors subserve only the tonic contractions.
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PMID:Differences in the effects of vasopressin and oxytocin on feline gastric corpus motility: selective action of vasopressin on longitudinal muscle. 964 34

Metabolites of the analogue 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin (carbetocin) following incubation with a rat kidney homogenate were isolated and their pharmacodynamic properties investigated. Apart from the parent compound two metabolites were identified namely desGlyNH2-carbetocin (carbetocin metabolite I) and desLeuGlyNH2-carbetocin (carbetocin metabolite II). Both carbetocin, carbetocin metabolite I and carbetocin metabolite II displayed binding affinities to the myometrial oxytocin receptor of a similar magnitude as oxytocin. Carbetocin was found to have agonistic properties on isolated myometrial strips and it was found to exert this effect through generation of inositol phosphates, as is the case for oxytocin. However, maximal contractile effect of carbetocin was approximately 50% lower than that of oxytocin (2.70 +/- 0.12 g compared to 5.22 +/- 0.26 g) and EC50 was approximately ten times higher (48.0 +/- 8.20 nM compared to 5.62 +/- 1.22 nM). Neither carbetocin metabolite I nor carbetocin metabolite II were able to contract isolated myometrial tissue. All three compounds displayed antagonistic properties against oxytocin in vitro, with carbetocin being the strongest inhibitor (pA2 = 8.21) and carbetocin metabolite II (pA2 = 8.01) being stronger than carbetocin metabolite I (pA2 = 7.81). These results indicate that carbetocin is a partial agonist/antagonist to the oxytocin receptor while the two metabolites carbetocin metabolite I and carbetocin metabolite II are pure antagonists. All three analogues bound to the myometrial vasopressin V1 receptor, albeit with much lower affinities than to the oxytocin receptor. Carbetocin metabolite II showed the weakest binding affinity of 33.7 +/- 7.34 nM compared to 7.24 +/- 0.29 nM for carbetocin and 9.89 + 2.80 nM for carbetocin metabolite I. Only carbetocin bound to the renal vasopressin V2 receptor though the binding affinity was very low (61.3 +/- 14.6 nM).
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PMID:Oxytocin receptor binding and uterotonic activity of carbetocin and its metabolites following enzymatic degradation. 976 35

[Arg8]vasopressin improved long-term retrieval processes and relearning in a go-no go visual discrimination task when bilaterally microinjected at a dose of 25 pg/animal into the ventral hippocampus of mice, 10 min prior to the retention session. We had shown that this enhancing effect is antagonized by pretreatment with equal or lower doses (25 pg or 1 ng) of the vasopressin V1 receptor antagonist, (d(CH2)5Tyr(Me)-vasopressin). The present study was an attempt to determine whether the vasopressin V2 receptor antagonist or oxytocin receptor antagonist is as effective as the vasopressin V1 receptor antagonist to block the behavioral effect of vasopressin in the ventral hippocampus. We tested the effect of 25 pg of [d(CH2)5-D-Ile2,Ile4,Arg8]vasopressin, a vasopressin V2 receptor antagonist, and [d(CH2)5,Tyr(Me)2,Thr4,Tyr-NH9(2)]ornithine vasotocin, an oxytocin receptor antagonist, under the same experimental conditions as those used to test the effect of the vasopressin V1 receptor antagonist. The results showed that the vasopressin V2 receptor antagonist microinjected into the ventral hippocampus did not alter the enhancing effect of vasopressin on retrieval and relearning. In contrast, the oxytocin receptor antagonist blocked the vasopressin-enhancing effect on retention processes. We can conclude from the data that both vasopressin V1 receptors and oxytocin receptors seem to be involved in the enhancing effect of vasopressin on memory retention. In contrast, the vasopressin V2 receptors do not seem to be involved in the effect of the peptide.
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PMID:The behavioral effect of vasopressin in the ventral hippocampus is antagonized by an oxytocin receptor antagonist. 986 5

Chimeric vasopressin V2/OT receptors were constructed and investigated to identify receptor regions involved in ligand binding or G protein coupling. The fusion sites for one series of hybrid receptors were either located at the C-terminal end of the third extracellular domain or in the centre of the third transmembrane helix, respectively. In each pair of the resulting symmetrical hybrids only one receptor was able to bind arginine vasopressin (AVP) and/or oxytocin (OT). In both cases a major part of the vasopressin V2 receptor (V2R) was needed for ligand binding. A chimeric OT/V2 receptor including OT receptor (OTR) sequences from its N-terminus to the middle of transmembrane region three showed both high-affinity OT binding (Ki = 3 nM) and activation of the adenylyl cyclase. In contrast, a hybrid containing OTR sequences reaching from transmembrane helix five to its C-terminus showed the V2 receptor's ligand binding profile and was unable to couple to G alpha s. These results indicate (i) that the third and/or the fourth intracellular domain of the V2R are involved in G protein coupling and (ii) for high-affinity OT binding the N-terminal third of the OTR plays an important role. By detailed binding studies on a second series of chimeric V2/OT receptors with AVP, OT and the two hybrid hormone derivatives arginine vasotocin and oxypressin it was further demonstrated that the first two extracellular domains of the OTR are involved in binding to the C-terminal tripeptide of OT. Moreover, the third extracellular domain of the OTR is able to contact the cyclic part of OT and the fourth outer domain does not interact with the two variable amino acid residues of AVP and OT. Thus, the first three extracellular domains of the OTR provide an essential part of the OT binding site. The other part is most probably contributed by the OTR's transmembrane helices 3 and 4. Photoaffinity labeling and ligand binding studies demonstrated that the binding site for the OT antagonist d(CH2)5[Tyr(Me)2, Thr4, Orn8, Tyr9]vasotocin is located in the helices 1, 2 and 7. Our results provide evidence for the existence of separate domains of a peptide hormone receptor involved in binding and selectivity for agonists and peptide antagonists.
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PMID:Identification of neurohypophysial hormone receptor domains involved in ligand binding and G protein coupling. 1002 28

The two neurohypophysial hormones arginine vasopressin (AVP) and oxytocin have actions in the inner medullary collecting duct (IMCD) where both peptides induce an increase in cAMP accumulation. The present study has employed a novel IMCD cell line to determine whether these two hormones induce cAMP accumulation via common or separate receptors, and to characterize the potential receptors responsible. Equal volumes of vehicle (150 mM NaCl) or hormone/antagonist solutions were added to aliquots of 10(4) IMCD cells in the presence of 10(-3) M 3-isobutylmethylxanthine (IBMX) and incubated at 37 degrees C for 4 min. cAMP levels were determined by radioimmunoassay and protein concentration by Bradford assay. Both AVP and oxytocin elicited dose-dependent increases in cAMP generation, though oxytocin was less potent than AVP (EC50 = 1.6 x 10(-8) M vs. 7.4 x 10(-10) M). AVP at 10(-8) M and oxytocin at 10(-8) M, concentrations sufficient to elicit near-maximal cAMP accumulation, resulted in cAMP levels of 73.4 +/- 1.7 and 69.0 +/- 3.3 pmol (mg protein)-1 (4 min)-1, respectively (n = 10), compared with the vehicle-treated basal value of 37.7 +/- 2.2 pmol (mg protein)-1 (4 min)-1 (P < 0.001, n = 10). Combined AVP (10(-8) M) and oxytocin 10(-6) M) resulted in cAMP accumulation of 63.8 +/- 3.1 pmol (mg protein)-1 (4 min)-1 (n = 10), which was not significantly different from the effect of oxytocin alone, but slightly less than that for AVP alone (P < 0.05). A submaximal concentration of AVP (10(-10) M) induced cAMP accumulation of 48.6 +/- 2.5 pmol (mg protein)-1 (4 min)-1 (P < 0.01 compared with basal level of 34.9 +/- 2.4 pmol (mg protein)-1 (4 min)-1, n = 10), which was blocked in the presence of a vasopressin V2 receptor antagonist (10(-7) M OPC-31260) but not by the oxytocin receptor antagonist (10(-6) M [Pen1,pMePhe2, Thr4,Orn8]oxytocin) (36.3 +/- 6.1 and 45.1 +/- 1.3 pmol (mg protein)-1 (4 min)-1 respectively, P < 0.05, n = 10). A submaximal concentration of oxytocin (10(-7) M) induced a cAMP accumulation of 45.8 +/- 1.8 pmol (mg protein)-1 (4 min)-1 (n = 10), which was reduced by addition of 10(-6) M oxytocin antagonist (36.3 +/- 2.1 pmol (mg protein)-1 (4 min)-1, P < 0.05, n = 10), whereas co-incubation with 10(-6) M of the V2 receptor antagonist had no effect (43.2 +/- 1.3 pmol (mg protein)-1 (4 min)-1, n = 10). These results indicate that AVP and oxytocin induce cAMP accumulation from a common ATP pool in IMCD cells, and that separate vasopressin V2 and oxytocin receptor systems are involved, perhaps coupled to a common adenylate cyclase system.
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PMID:Separate receptors mediate oxytocin and vasopressin stimulation of cAMP in rat inner medullary collecting duct cells. 1008 3


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