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)

An oxytocic antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid,2-O-methyltyrosine,4-threonine, 8-ornithine,9-tyrosylamide]vasotocin (d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH2(9)]OVT [corrected], was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. 125I-labelling was performed with 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl-glycoluril. Iodination resulted in an increased affinity for rat uterine oxytocin receptors. A considerably lower affinity for rat vascular V1- and renal V2-receptors was found, resulting in a highly specific oxytocin receptor ligand. 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT [corrected] was demonstrated to bind selectively to one population of binding sites in rat uterus and ventral hippocampal membrane preparations. Dissociation constants ranged between 0.03 and 0.06 nM. After 3 days of exposure autoradiography revealed binding in regions known to contain oxytocin receptors as well as labelling in some new regions, while no binding was found in the lateral septum, a structure containing mainly [8-arginine]vasopressin receptors. The high specific radioactivity of 125I-labelling allowed important reductions in membrane protein amount, gain in precision of binding analysis as well as considerably lower exposure times for autoradiography.
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PMID:125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT: a selective oxytocin receptor ligand. 283 49

Three binding sites have been recently reported on the rat, calf and sheep myometrial cells, with dissociation constants (Kd) roughly 10(-9), 10(-7) and 10(-5) mol/l. Oxytocin receptor for the uterotonic response in vitro was identified pharmacologically: 1) The analysis of dose-response curves has been based on a partial irreversible inhibition of the receptor on isolated rat uterus by the method of Furchgott and Bursztyn, and by the newly suggested plotting of Kd vs. maximal response for an increasing degree of irreversible inhibition. 2) pA2- values (reflecting Kd) of structural analogues of oxytocin acting as competitive inhibitors of the parent hormone have been analysed according to Free and Wilson. Contribution of side chains in individual positions of the nonapeptide chain were computed, tested on additivity and then used for back-computation of a Kd for oxytocin. Results of all experiments reveal a Kd for oxytocin receptor (rat uterus in vitro) of 2 x 10(-7) mol/l. Possible endocrine functions of the high and low affinity sites have not been clarified as yet.
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PMID:Pharmacological approaches to the identification and classification of myometrial oxytocin receptors. 283 18

The levels of oxytocin receptor (OTR), cytosolic progestin receptor (cPR), cytosolic and nuclear estrogen receptor (cER, nER) were measured in the endometrium of 28 heifers that had been slaughtered on a defined day of the estrous cycle. In an additional, trial endometrial tissue obtained from 78 heifers or cows at the abattoir was analysed for OTR. OTR was absent during the luteal phase (after day 6), but a minor elevation was observed after day 15. OTR increased rapidly after luteolysis on days 17-18 reaching a maximum during estrous on day 21, and decreased again during days 1-6. cER and cPR were different to OTR but followed a similar pattern with maximal levels during days 1-8 of the estrous cycle. At day 12 both receptors were minimal and increased again towards day 21. nER was maximal at day 19-21 coinciding with maximal estradiol levels and estrous. Our data indicate that owing to an increasing sensitivity of the endometrium to progesterone and estradiol after day 12, these steroids may be mainly responsible for the initiation of first PGF2 alpha surges and luteolysis. Oxytocin seems to be of minor importance at this stage owing to low sensitivity of the endometrium for oxytocin.
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PMID:Dynamics of oxytocin, estrogen and progestin receptors in the bovine endometrium during the estrous cycle. 283 97

Oxytocin at a physiological concentration stimulated the immediate release of free arachidonic acid from dispersed human decidual cells in a perfusion system. This indicates that oxytocin activates phospholipase(s) thus enhancing prostaglandin synthesis. The effect of oxytocin on the release of [3H]-arachidonic acid from decidual cells of women in labor was significantly greater (1036 +/- 207, mean dpm +/- SEM, n = 23) than from those of women not-in-labor (505 +/- 121 dpm, n = 12) or with endometrial cells of non-pregnant women (711 +/- 210 dpm, n = 18), and correlates well with reported oxytocin receptor concentrations in these tissues. These new findings are consistent with a role for endogenous oxytocin in stimulating prostaglandin synthesis at the onset of parturition.
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PMID:Oxytocin stimulates the release of arachidonic acid and prostaglandin F2 alpha from human decidual cells. 284 Jun 90

Binding of [3H]oxytocin to purified myometrial plasma membranes was unaffected by continuous infusion of bradykinin over 5 days in rats pretreated with oestradiol 2 days before collection of tissue. In contrast, oxytocin treatment resulted in a 76% decrease in maximal binding of [3H]oxytocin and thereby in oxytocin receptor concentration without affecting the dissociation constant. The KM value (molar concentration giving half maximal contraction) of isolated uterine strips stimulated with oxytocin was increased and maximal contractile responses were reduced following oxytocin infusions. The binding of [3H]bradykinin to purified plasma membranes was influenced by treatment with both oxytocin and bradykinin. Bradykinin infusions down-regulated the bradykinin receptor concentration by 19%, while the receptor affinity remained unchanged. Maximal contraction (Emax) values of isolated strips stimulated with bradykinin exhibited a slightly attenuated response and KM values were significantly enhanced. Long-term treatment with oxytocin down-regulated myometrial bradykinin receptors by 31%. In addition, oxytocin infusions caused Emax to decrease and KM to increase in experiments with isolated uterine strips stimulated with bradykinin. It is concluded that the down-regulation of oxytocin and bradykinin receptors following prolonged exposure to oxytocin may result from changes in a common pathway for intracellular peptide receptor processing. Likewise, the increased KM values of isolated myometrial strips (despite unchanged dissociation constants) suggest that prolonged oxytocin treatment affects the coupling between receptor activation and contractile response.
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PMID:Receptor-binding characteristics and contractile responsiveness of the myometrium following prolonged infusion of bradykinin and oxytocin in rats. 284 29

Purified myometrial plasma membrane fractions were prepared from rats treated with oestradiol to induce oestrus. The binding affinities of 11 antagonistic oxytocin analogues to the oxytocin receptor of the plasma membranes were measured. Furthermore, lipophilicity of the peptides was assessed by reversed-phase high pressure liquid chromatography. No significant correlation was found between lipophilicity of the analogues and values for antagonistic potencies or binding affinities. Also, receptor-binding affinity did not correlate with in-vitro antagonistic activity whereas a significant correlation was obtained between binding affinities and in-vivo antagonistic potency for analogues void of partial agonist properties. It is concluded that neither receptor affinity nor lipophilicity in the analogues can predict the potency of the antagonists in vitro. However, receptor affinity was found to be a relatively good predictor of the in-vivo potency, while the usefulness of measuring antagonistic potency in vitro is questioned.
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PMID:Correlation between myometrial receptor affinity, lipophilicity and antagonistic potency of oxytocin analogues in the rat. 284 47

Synthesis of the uterine receptor for the hypothalamic hormone oxytocin has been induced in oocytes from Xenopus laevis previously primed with bovine endometrium mRNA. The injected oocytes responded to oxytocin by showing dose-dependent oscillations in membrane currents as recorded by the voltage-clamp method. The response was specific in that it was not elicited by several other peptides tested. The oxytocin-induced membrane changes were suppressed when oocytes were pretreated with an oxytocin receptor antagonist.
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PMID:Functional expression of the oxytocin receptor in Xenopus laevis oocytes primed with mRNA from bovine endometrium. 285 10

A new, highly selective radio-iodinated oxytocin receptor antagonist [( 1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid, 2-O-methyltyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]-vasotocin) was used to identify and quantitate specific binding sites for the neurohypophyseal hormone oxytocin with in vitro incubation of rat brain sections and autoradiography. Exclusively oxytocin binding sites were detected in view of the high affinity of the [125I]-labelled oxytocin antagonist for oxytocin binding sites and the negligible affinity for the vasopressin liver (V1) and kidney (V2) receptor types. The putative oxytocin receptors were abundantly present in several brain regions, where previously discrimination between oxytocin and vasopressin binding was difficult, i.e. the olfactory nucleus, the islands of Calleja, the ventromedial nucleus of the hypothalamus, the central amygdaloid nucleus and the ventral subiculum of the hippocampus. In addition oxytocin receptors were demonstrated in other areas, such as the taenia tecta, dorsolateral caudate putamen, ventral pallidum, accumbens, lateral septum, bed nucleus of the stria terminalis, thalamic paraventricular nucleus, lateral, basolateral and medial amygdala, the dorsal subiculum, perirhinal cortex and the amygdaloid-hippocampal area. The high affinity and the low detection threshold of this [125I]-labelled oxytocin antagonist permitted identification of oxytocin receptors in new regions such as the ventral part of the lateral septum, medial septum, dorsal motor nucleus of the vagus nerve and the olive nuclei in the brain stem.
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PMID:Topography of the oxytocin receptor system in rat brain: an autoradiographical study with a selective radioiodinated oxytocin antagonist. 285 12

Specific binding of [3H]oxytocin to high affinity sites (hormone receptors) in membrane preparations from uterine tissues of the ewe has been determined at varying stages of the oestrous cycle and in pregnancy. Mean receptor concentrations in caruncular and intercaruncular endometrium and in myometrium were 14.2, 1.9 and 13.0 fmol/mg protein respectively between days 10 and 13 of the cycle. By the day of oestrus these values had increased to 749, 1085 and 179 fmol/mg protein. These increases in receptor concentrations coincided with luteolysis and falling plasma progesterone levels and followed the preovulatory decline in peripheral oxytocin and rise in ovarian venous oestradiol-17 beta. Receptor concentrations were low in all uterine tissues from pregnant animals between days 14 and 19 after oestrus. Analysis of binding parameters by Scatchard plot suggested a single population of receptor molecules in each of the tissues studied with apparent dissociation constants in the range 1.9-2.2 nmol/l. A number of naturally occurring neurohypophysial peptides inhibited binding of [3H]oxytocin to the receptor from ewes at oestrus; the cross-reactions of arginine vasopressin and vasotocin exceeded that of oxytocin. Use of a receptor binding assay to measure oxytocin in extracts of corpora lutea on days 4 and 10 after oestrus gave values similar to those obtained by radioimmunoassay, suggesting the absence of other receptor-active peptides in the corpus luteum. It is concluded that the oxytocin receptor is present in both components of the endometrium, as well as in the myometrium and that changes in uterine receptor concentrations before oestrus are consistent with receptor activation by steroid hormones.
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PMID:Endocrine control of uterine oxytocin receptors in the ewe. 299 14

Continuous intravenous infusion of oxytocin (3 micrograms/h) between Days 13 and 21 after oestrus delayed return to oestrus by 7 days (length of cycle 23.3 +/- 0.6 days compared to 16.6 +/- 0.2 days in control ewes). At a lower infusion rate (0.3 micrograms/h) oxytocin delayed luteolysis in only 2 of 5 ewes. Treatment from Day 14, when luteolysis had already begun, was ineffective. Delay of luteal regression by oxytocin had no effect on the length of subsequent cycles. Measurement of circulating progesterone concentrations and luteal weight showed that prolongation of the oestrous cycle was due to prevention of luteal regression. Luteal regression and behavioural oestrus were induced during continuous oxytocin administration begun on Day 13 when cloprostenol was given on Day 15 (mean cycle length, 17.3 +/- 0.21 days). Continuous oxytocin infusion from Day 13 blocked the rise in uterine oxytocin receptor concentrations which normally precedes oestrus. Mean receptor concentrations in caruncular and intercaruncular endometrium and in myometrium were 76, 36 and 9 fmol/mg protein on Day 17 in ewes receiving continuous oxytocin (3 micrograms/h); in control ewes these values were 675, 638 and 130 fmol/mg protein respectively at oestrus. Receptor concentrations on the day of oestrus in ewes receiving oxytocin and cloprostenol were not significantly different from those in control ewes (649, 852, and 109 fmol/mg protein respectively). Since cloprostenol, a PGF-2 alpha analogue, overcame the antiluteolytic action of oxytocin, it is suggested that continuous oxytocin treatment may inhibit uterine production of PGF-2 alpha, possibly by down regulating the uterine oxytocin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous infusion of oxytocin prevents induction of uterine oxytocin receptor and blocks luteal regression in cyclic ewes. 299 86


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