UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Centrally administered oxytocin has been reported to facilitate affiliative and social behaviours, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3' untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma.
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PMID:Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3. 757 68

To investigate the effect of cholesterol on the oxytocin receptor function in myometrial membranes, we developed a new method to alter the membrane cholesterol content. Using a methyl-substituted beta-cyclodextrin, we were able to selectively deplete the myometrial plasma membrane of cholesterol. Vice versa, incubating cholesterol-depleted membranes with a preformed soluble cholesterol-methyl-beta-cyclodextrin complex restored the cholesterol content of the plasma membrane. Binding experiments showed that, with the removal of cholesterol from the membrane, the dissociation constant for [3H]oxytocin is enhanced 87-fold (from Kd = 1.5 nM to Kd = 131 nM), therefore shifting the oxytocin receptor from high to low affinity. Increasing the cholesterol content of the cholesterol-depleted membrane again restored the high-affinity binding (Kd = 1.2 nM). The presence of 0.1 mM GTP gamma S did not significantly change the number of high-affinity binding sites for [3H]oxytocin in native plasma membranes, in membranes depleted of cholesterol, and in plasma membranes with restored cholesterol content. The number of high-affinity binding sites for the oxytocin antagonist [3H]PrOTA was dependent in the same way on the cholesterol content as for [3H]oxytocin. Substitution of the membrane cholesterol with other steroids showed a strong dependence of the oxytocin receptor function on the structure of the cholesterol molecule. The detergent-solubilized oxytocin receptor was not saturable with [3H]oxytocin even at concentrations up to 10(-6) M of radioligand. Addition of the cholesterol-methyl-beta-cyclodextrin complex to the detergent-solubilized oxytocin receptor induced a saturation of the solubilized binding sites (Bmax = 0.98 pmol/mg) for oxytocin (Kd = 16 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor. 757 71

We have expressed a c-myc epitope-tagged human oxytocin receptor in the baculovirus/Sf9 cell system. The receptor was identified by SDS-PAGE and subsequent immunoblot as a approximately 50 kDa protein which decreased to about 44 kDa upon treatment with tunicamycin. Binding studies showed that the human oxytocin receptor was expressed in a low-affinity state (Kd = 215 nM; Bmax = 1.66 pmol/mg). After addition of cholesterol in the form of a soluble cholesterol-methyl-beta-cyclodextrin complex to the membranes, we obtained part of the human oxytocin receptor in its high-affinity state for oxytocin (Kd = 0.96 nM and Bmax = 318 fmol/mg of protein). In subsequent studies, we added the cholesterol-methyl-beta-cyclodextrin complex to the Sf9 cell culture medium at various times post infection. Binding analysis showed that this results in a more than 3-fold further increase in functional receptor binding sites of high-affinity state (Bmax = 1.08 pmol/mg). The cholesterol effect was dose-dependent, with an EC50 of about 50 microM cholesterol. Due to these findings, we determined the cholesterol and phospholipid content in purified Sf9 plasma membranes. The untreated naturally cholesterol auxotroph insect cells grown in medium with 2% fetal calf serum had a molar cholesterol/phospholipid ratio of about 0.04, which is approximately 20-fold lower than normally found in plasma membranes of higher eukaryotic cells. The high-affinity binding of the oxytocin receptor increased in parallel with the cholesterol levels present in the corresponding plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. 757 72

The peptide hormone oxytocin is produced both in the hypothalamus and in certain peripheral organs. The extent of extra-hypothalamic hormone synthesis in the pregnant cow has not previously been examined. In this study we have analyzed different tissues from the pregnant bovine reproductive tract and corpus luteum for the presence of mRNA encoding the oxytocin peptide as well as the oxytocin receptor. In uterine tissues oxytocin mRNA could only be detected sporadically with the help of a reverse transcription-polymerase chain reaction method, implying only very low levels of expression. The caruncles showed a consistently low level of oxytocin gene expression, which appeared up-regulated at term. However, in the corpus luteum there was a significant level of oxytocin gene expression at term, particularly following the onset of labor. The transcript levels were sufficiently high to be measurable by both RNase protection assay and by Northern hybridization; these levels imply a rescue of the oxytocin gene expression seen in the corpora lutea of cyclic and early pregnant cows. At the peptide level this expression was confirmed by immunohistochemistry. A sensitive RNase protection assay was developed to detect transcripts encoding the oxytocin receptor. Transcripts were detected in most uterine tissues, including the caruncles, with highest levels in the endometrium and myometrium at term. No transcripts could be detected in the corpus luteum at any stage of pregnancy, nor in the amnion. The results suggest the possibility of local, paracrine effects of oxytocin within the uterus of the pregnant cow. The rescue of luteal oxytocin at term could act to supplement the circulating hormone of pituitary origin.
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PMID:Oxytocin and oxytocin receptor gene expression in the reproductive tract of the pregnant cow: rescue of luteal oxytocin production at term. 757 79

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.
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PMID:Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment. 758 81

Endometrial oxytocin receptor concentrations and oxytocin-induced plasma concentrations of 13,14,dihydro-15-keto prostaglandin F2 alpha were investigated on days 14 and 17 of the oestrous cycle and on days 14, 17, 25, 65, 85 and 145 of gestation in ewes. Total 13,14,dihydro-15-keto prostaglandin F2 alpha release in response to a bolus injection of oxytocin was significantly (P < 0.05) higher at luteolysis (day 17 of the oestrous cycle) than at any other stage of the oestrous cycle or in early gestation. On days 65, 85 and 145 of gestation, total prostaglandin release was significantly (P < 0.05) increased compared with earlier in gestation. Maximum concentrations of 13,14,dihydro-15-keto prostaglandin F2 alpha in response to oxytocin followed a similar pattern. Oxytocin receptor concentrations reflected total oxytocin-induced 13,14,dihydro-15-keto prostaglandin F2 alpha release, with increased oxytocin receptor concentrations occurring on day 17 of the oestrous cycle, compared with those observed on day 14 of the oestrous cycle and on days 14, 17 and 25 of gestation. By day 65 of gestation, oxytocin receptor concentrations were again increased. However, on days 85 and 145 of gestation, oxytocin receptor concentrations had decreased to concentrations similar to those observed in early gestation. These results indicate that oxytocin-induced 13,14,dihydro-15-keto prostaglandin F2 alpha release during early gestation is minimal despite the presence of endometrial oxytocin receptors. In mid-gestation, oxytocin-stimulated 13,14,dihydro-15-keto prostaglandin F2 alpha release is increased with a concomitant increase in uterine oxytocin receptor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin-induced prostaglandin F2 alpha release and endometrial oxytocin receptor concentrations throughout pregnancy in ewes. 761 95

The aim of the present study was to characterize vasopressin receptors within the two circumventricular organs located in the lamina terminalis of the rat brain, namely the organum vasculosum of the lamina terminalis and the subfornical organ. Cells derived from both structures were isolated, cultured and intracellular Ca2+ concentrations were measured in single fura-2 loaded neurons and astrocytes after application of vasopressin and various vasopressin analogues. Subsequent to Ca2+ measurements, the identification of neurons and astrocytes was verified using immunocytochemistry with cell type-specific antibodies. High proportions of subfornical organ (34%) and organum vasculosum laminae terminalis (28%) neurons exhibited increased intracellular Ca2+ concentration after exposure to 1-1000 nM vasopressin. Within single cells, the response was dose-dependent. Similar results were obtained in subfornical organ (62%) and organum vasculosum laminae terminalis (38%) astrocytes with minor differences in the transient amplitude and pattern distribution when compared with neurons. Since omission of extracellular Ca2+ preserved vasopressin responsiveness, it is likely that intracellular stores were the main source of mobilized Ca2+. The preincubation of neurons and astrocytes with the V1 receptor-specific antagonist d(CH2)5[Tyr(Me)2]8-arginine vasopressin (10-100 nM) selectively and reversibly blocked the vasopressin-mediated response. Oxytocin-induced Ca2+ transients (0.32-1000 nM), which were observed in 32% (63%) or organum vasculosum laminae terminalis and in 54% (42%) of subfornical organ neurons (astrocytes), were not affected by the V1-specific antagonist. These data indicate the presence of a V1-like vasopressin receptor and an oxytocin receptor in cultured neurons and astrocytes from both circumventricular organ structures. In addition, the exposure to the highly selective V2 receptor agonist, 1-desamino,8-D-arginine vasopressin, evoked Ca2+ transients almost exclusively in organum vasculosum laminae terminalis neurons (eight of 18 tested). Only 1 (n = 14) subfornical organ neuron and none of the astrocytes tested (n = 26) responded to 1-desamino,8-D-arginine vasopressin. Since 1-desamino,8-D-arginine vasopressin acting via "classical" V2 receptors is not expected to affect the intracellular Ca2+ concentration, these data indicate the tissue and cell type-specific expression of a 1-desamino,8-D-arginine vasopressin-sensitive vasopressin receptor in neurons of the organum vasculosum laminae terminalis. In summary, the results indicate a heterogeneity of neurohypophyseal peptide receptor subtypes in the primary cell culture of both circumventricular structures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of vasopressin receptors in cultured cells derived from the region of rat brain circumventricular organs. 761 68

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.
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PMID:Involvement of beta-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and alpha-melanocyte-stimulating hormone, in rats. 761 71

Changes in OR mRNA expression in the ventromedial hypothalamus (VMH) in relation to the estrous cycle were measured by in situ hybridization with a rat oxytocin receptor (OR) probe. Binding studies have localized ORs to various brain regions, and have detected a high density of receptors in the VMH, a nucleus containing large numbers of estrogen responsive neurons. Previous studies in this lab have reported a significant increase in OR mRNA expression in the VMH in ovariectomized rats treated with estrogen. The present study was designed to determine whether changes in steroid hormone levels across the estrous cycle result in induction of OR mRNA expression. Autoradiographic studies revealed differences in OR mRNA expression in the rostral and caudal as well as medial and lateral aspects of the VMH. OR mRNA levels were highest in the caudal portion of the vIVMH on the afternoon (16:00 hr) of proestrus. The rostral region exhibited a high level of expression in the ventrolateral region of the VMH on the morning (9:00 hr) of proestrus and in the dorsomedial region of the VMH on the afternoon of proestrus. Little or no OR mRNA expression was evident in the rostral or caudal VMH on the morning or evening of diestrus. These results support previous findings which showed a regulation of OR binding by gonadal steroids and suggest that this may be due to altered expression of the OR gene. These effects suggest a possible role of ORs in the oxytocin stimulated release of luteinizing hormone.
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PMID:Oxytocin receptor mRNA expression in the ventromedial hypothalamus during the estrous cycle. 762 34

During luteal regression episodic pulses of oxytocin secretion become coupled to the release of prostaglandin F2 alpha (PGF2 alpha) following synthesis of endometrial oxytocin receptors, but in early pregnancy the inhibition of oxytocin receptor formation by the conceptus prevents the development of the pulsatile pattern of PGF2 alpha release needed to achieve luteolysis. Oxytocin receptors are present on the luminal epithelium in ovariectomized and anoestrous ewes, in pregnant animals throughout most of gestation (day 21 to term) and in explants of endometrial tissue cultured in vitro. These receptors can be downregulated for a brief period by progesterone (10-12 days in sheep, 12-14 days in cattle). This period of inhibition can be extended by infusion of interferon tau (IFN-tau) (which probably inhibits oxytocin receptor gene transcription) or of oxytocin into the systemic circulation (which may act further downstream, possibly at the level of translation). Oxytocin receptors also develop on the caruncular stroma and deep glands at oestrus, but these need positive upregulation and appear dependent on an oestrogenic environment. Only epithelial receptors are needed to achieve a maximal PGF2 alpha response to an oxytocin challenge, but the presence of oxytocin receptors does not necessarily confer responsiveness as other factors may influence intracellular coupling mechanisms and precursor availability. The duration of the luteal phase is regulated by the time of the initial post-ovulatory rise in progesterone and the duration of exposure to progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The oxytocin receptor, luteolysis and the maintenance of pregnancy. 762 43

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