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

The question as to whether calcium can be considered to be a mediator of oxytocin-induced myometrial contraction has been investigated. Assuming that the contraction is linearly proportional to the myoplasmic calcium concentration, several possible molecular mechanisms leading to its increase (calcium release from the cell membrane, acceleration of calcium transport from extracellular space by a 'gate' mechanism, release from intracellular organelles, blockade of calcium pumps) were modelled on an analog computer. The oxytocin intervention in the calcium distribution was mimicked by a discontinuous change of the appropriate rate constants. The computed transient simulating the myoplasmic calcium concentration was then compared with an experimental time profile of uterine tension. The result of screening the models shows that oxytocin must act predominantly via release of calcium bound to the cell membrane. A quantitative comparison, however, requires that the kinetics of oxytocin distribution in myometrium also be considered in the model. The problem treated in this paper demonstrates the possibilities and limitations of a screening procedure based upon direct comparison of time profiles of experimental processes with several computed model alternatives.
Mol Cell Endocrinol 1977 Feb
PMID:The use of dynamic models to study the role of calcium in the oxytocin-induced contractions of the uterus. 19 65

Direct measurements of cyclic AMP were performed in the isolated epithelium of frog skin. Phosphodiesterase inhibitors (methylxanthines, papaverine) and activators of adenylyl cyclase (oxytocin, catecholamines) significantly increased the cyclic AMP content. Propranolol completely blocked the generation of cAMP induced by beta-adrenergic agonists but had little or no effect on that induced by oxytocin. Phentolamine enhanced the cAMP production by adrenalin and noradrenalin. At supramaximal concentrations, oxytocin and isoproterenol produced similar increments in cAMP, while exposure to both agents roughly doubled the increase in cAMP. The results suggest the presence of independent receptors for oxytocin and catecholamines in frog skin, with additive effects on cAMP generation.
Mol Cell Endocrinol 1978 Jun
PMID:Cyclic AMP levels in isolated frog skin epithelium: effects of phosphodiesterase inhibitors, oxytocin and catecholamines. 21 57

Treatment of unanesthetized castrated adult male rats every 3 h for 48 h with either 5 microgram of arginine vasotocin (AVT) and/or 1 microgram luteinizing hormone-releasing hormone (LRH) caused a significant inhibition of plasma levels of luteinizing hormone (LH) and compared to castrated control rats receiving diluent only. However, the intravenous (iv) injection of 1 microgram of AVT into urethane-anesthetized male rats which had been castrated for 0, 24 or 48 h did not affect plasma levels of LH at 10, 20 or 60 min following injection compared to their respective diluent-treated castrated control rats. Similarly, the iv injection of either 100 ng, 1 microgram or 10 microgram AVT was unable to acutely affect plasma levels of LH in intact male rats. Following the iv injection of 2 doses of 50 ng LRH spaced 1 h apart in anesthetized castrated male rats, 2 peaks of equal magnitude in plasma LH were noted. Castrated rats treated with 2 injections spaced 1 h apart of LRH + AVT had significantly higher plasma levels of LH than did rats treated with LRH alone. In subsequent studies, both AVT and arginine vasopressin were observed to augment the plasma response of LH to an injection of LRH whereas oxytocin had no effect. A single injection of AVT + LRH significantly augmented the plasma titers of LH compared to levels observed in LRH-treated control rats as did a second injection 1 h later. The administration of cyproterone acetate sc for 2 days by itself had no effect on plasma LH but in conjunction with LRH caused a marked rise in plasma LH compared to intact rats treated with LRH alone. AVT in combination with LRH and cyproterone acetate caused a significant elevation in plasma LH at 60 min post-injection when compared to plasma levels of rats treated with LRH alone or the combination of LRH and cyproterone acetate. It is concluded that acute intravenous injections of AVT augment the LH-releasing activity of LRH; chronic treatment for 48 h, however, with LRH + AVT leads to a significant depression of plasma LH perhaps due to an exhaustion of the releasable pool of LH in the anterior pituitary.
Mol Cell Endocrinol 1979 Apr
PMID:Interaction of luteinizing hormone-releasing hormone, cyproterone acetate and arginine vasotocin on plasma levels of luteinizing hormone in intact and castrated adult male rats. 37 36

Two series of neurohypophysial peptide amino-acylated derivatives were tested for their ability to activate plasma membrane adenylate cyclase prepared from pig or rat kidney. They were firstly [8-lysine]-vasopressin-related derivatives (Na-[Glycyl-Cys]1-[8-Lysine]-vasopressin and Na-[Glycyl-Glycyl-Cys51-[8-Lysine]-vasopressin) and secondly oxytocin-related derivatives (Na-[Glycyl-Cys-a1)-oxytocin, Na-[Leucyl-Glycyl-Glycyl--Cys]-oxytocin, and Na-[Glycyl-Cys]-[2-0methyl tyrosine]-oxtocin). The maximal adenylate cyclase activation induced by these peptides was lower than that induced by their respective parent hormones. After incubation of these analogues with plasma membranes obtained from the renal medulla, no significant release of parent hormones occurred. Good qualitative correlations were observed between relative antidiuretic activities measured in vivo and relative potencies in activating adenylate cyclase. It was concluded that direct action of peptides tested on the kidney is at least partly responsible for their antidiuretic activity in vivo.
Mol Cell Endocrinol 1975 Jan
PMID:Renal adenylate cyclase activation by amino acylated vasopressin and oxytocin. 114 16

Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels, and it is suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Biochem 1992 Sep 08
PMID:Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus. 128 Dec 64

In order to evaluate the changes in uterine oxytocin receptor-specific mRNA during pregnancy, receptor expression in Xenopus oocytes are examined electrophysiologically following microinjection of mRNA from human uterus. In voltage-clamped oocytes injected with term myometrial mRNA, oxytocin elicited an inward current response. The amplitude of the oxytocin-induced current increased with increasing dose of oxytocin, but no current was elicited following stimulation with vasopressin. The oxytocin-induced current was completely eliminated as a result of pretreatment with a specific oxytocin antagonist. 21 of 27 oocytes injected with term myometrial mRNA showed a large amplitude (77.0 +/- 16.1 nA) reaction to oxytocin. In comparison, only 3 of 13 oocytes injected with early gestational myometrial mRNA exhibited a small amplitude (4.6 +/- 1.4 nA) reaction to oxytocin. No oxytocin response was observed in oocytes injected with non-pregnant myometrial mRNA. These results indicate that the striking increment in oxytocin sensitivity in term uterus depends on the increase in mRNA encoding oxytocin receptors.
J Steroid Biochem Mol Biol 1992 May
PMID:Estimation by an electrophysiological method of the expression of oxytocin receptor mRNA in human myometrium during pregnancy. 131 33

Numerous studies have implicated opioids in the regulation of hypothalamic functions. Dynorphin, which is co-expressed with vasopressin in the magnocellular neurons of the paraventricular and supraoptic nuclei, is co-regulated with vasopressin in response to hyperosmolality and appears to inhibit vasopressin and oxytocin release from the posterior pituitary. Enkephalin is present in paraventricular parvocellular neurons and its expression is elevated in response to various stresses. However, enkephalin's presence and roles in paraventricular and supraoptic magnocellular neurons are uncertain. By giving rats daily intraperitoneal injections of hypertonic saline for up to 12 days, we induced a marked increase in enkephalin expression in magnocellular neurons of the paraventricular and supraoptic nuclei, beyond what develops from drinking hypertonic saline. Our results suggest that enkephalin expression in both vasopressin and oxytocin neurons may increase in response to chronic stresses and provide another source of enkephalin in addition to the parvocellular neurons.
Brain Res Mol Brain Res 1992 Mar
PMID:Chronic stress elevates enkephalin expression in the rat paraventricular and supraoptic nuclei. 134 19

1. Using an immunocytochemical procedure a wide range of immunoreactive vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin, neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a correlation between hemocyte and APUD cells and is evidence of a relationship between the neuroendocrine and the immune systems.
Cell Mol Neurobiol 1992 Oct
PMID:The presence of immunoreactive vertebrate bioactive peptide substances in hemocytes of the freshwater snail Viviparus ater (Gastropoda, Prosobranchia). 136 24

In the guinea pig myometrium, carbachol, oxytocin, and fluoroaluminates stimulated the breakdown of phosphatidylinositol 4,5-bisphosphate, which was insensitive to pertussis toxin [Biochem. J. 255:705-713 (1988)]. We now demonstrate that an increased accumulation of inositol phosphates, with an early production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], could also be obtained with K+ (30 mM) and the Ca2+ ionophore ionomycin. Removal of extracellular Ca2+ or addition of the Ca2+ channel antagonists nifedipine and verapamil almost totally abolished stimulations elicited by high K+ and partially attenuated receptor- and fluoroaluminate-mediated increases in inositol phosphates. Isoproterenol similarly attenuated the accumulation of inositol phosphates elicited by carbachol, oxytocin, and fluoroaluminates (maximal inhibition, 35%; EC50, 0.5 nM), with no change in the rate of Ins(1,4,5)P3, inositol bisphosphate, and inositol monophosphate generation. The beta-adrenergic receptor-induced inhibition was prevented by pertussis toxin and could not be reproduced by forskolin, indicating that cAMP was not involved. Experimental findings were, rather, consistent with a predominant role for Ca2+. Thus, inhibition due to isoproterenol was lost in a Ca(2+)-depleted medium and was not additive with that caused by nifedipine. Accumulation of inositol phosphates triggered by high K+ was insensitive to the beta-adrenergic receptor inhibition. The inhibitory effect of isoproterenol, similar to that of nifedipine, was counteracted by ionomycin and also by the Ca2+ channel agonist Bay K 8644. These data indicate that in the myometrium 1) phospholipase C can be activated through a voltage-gated Ca2+ entry-dependent process that contributes at least partially to the stimulations triggered by receptor- and/or guanine nucleotide-binding protein-mediated activation and 2) beta-adrenergic receptor activation is linked via a cAMP-independent, pertussis toxin-sensitive pathway to an inhibition of voltage-gated Ca2+ channels, resulting in an attenuation of the Ca(2+)-associated generation of inositol phosphates.
Mol Pharmacol 1992 Mar
PMID:Activation of beta-adrenergic receptors inhibits Ca2+ entry-mediated generation of inositol phosphates in the guinea pig myometrium, a cyclic AMP-independent event. 137 85

The effects of adding oxytocin (OT) and arginine-vasopressin (AVP) on progesterone and estradiol-17 beta secretion by bovine granulosa cells in culture were studied. The influence of these steroids on OT and AVP release was also evaluated. OT (1, 10, 100 or 1000 mIU/ml) stimulates both progesterone and estradiol output. Small doses (10 pM/ml) of exogenous progesterone or estradiol stimulated a surge in OT, while the intermediate doses (100 or 1000 pM/ml) had no influence, and large doses (10,000 pM/ml) inhibited OT secretion by granulosa cells. Thus, a potential regulatory loop between OT and steroid hormone release by granulosa cells was demonstrated. Stimulation of a surge in steroids by OT, activation of OT release by small doses of steroids and inhibition of OT secretion by excess steroids may suggest the existence of a feedback mechanism regulating these hormones production. Addition of AVP (1, 10, 100 or 1000 pM/ml) inhibited progesterone and stimulated a surge in estradiol, while steroid hormones did not induce AVP release. These data suggest the regulation of ovarian steroidogenesis by AVP, feedback influences are less likely.
J Steroid Biochem Mol Biol 1992 Nov
PMID:The interrelationships between nonapeptide and steroid hormones secretion by bovine granulosa cells in vitro. 141 88


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