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

Effects of estradiol on the release of prostaglandin-like substance (PG) from rat uterus was investigated. The amount of PG released into a medium that did not contain oxytocin was decreased by estradiol, but the release of PG was remarkably increased by the addition of oxytocin. No significant correlation was found in the relationship between PG release and uterine contraction in uterus of either the ovariectomized rat and that of the estradiol-injected rat. The amount of PG released from the uterus of ovariectomized rat and the uterus of 6 hours after estradiol injection was decreased by indomethacin. The PG release promoting action of oxytocin observed in estradiol-injected rat uterus disappeared completely with treatment of phospholipase C.
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PMID:Effects of estradiol and oxytocin on the release of prostaglandin-like substance from isolated rat uterus. 74 8

A technique has been developed for prelabelling and permeabilisation of guinea pig uterine myocytes to enable measurement of arachidonic acid release/phospholipase A2 activity in cells with intact membranes. Intact cells were prelabelled with [3H]inositol or [3H]arachidonic acid for measurement of phospholipase C and A2 respectively. In intact cells 10 nM endothelin-1 or 1 microM bradykinin stimulated both inositol polyphosphate and arachidonic acid release, whilst 1 microM oxytocin, arginine vasopressin or histamine were without effect. In Streptolysin-O permeabilised myometrial cells calcium-stimulation of inositol polyphosphate and arachidonic acid release was detected between 10 microM and 1 mM free calcium. The patterns of inositol polyphosphate and arachidonic acid release were broadly similar. Responses to 1 mM calcium were not detected in intact cells not treated with Streptolysin-O. For arachidonic acid release the K0.5 for calcium activation was about 7 microM, a level above that normally likely to be found in the uterine myocyte. Hence it is concluded that unless there are high local concentrations of calcium close to the plasma membrane, calcium is unlikely alone to be the primary regulator of arachidonic acid release and phospholipase A2.
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PMID:Measurement of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. 130 78

In a previous report we demonstrated the presence of a vasotocin (AVT)-like peptide in chromaffin cells of the amphibian adrenal gland and showed that synthetic AVT is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. In the present study we evaluated the relative potency of various AVT analogs and investigated the mechanism of action of AVT on frog interrenal (adrenal) tissue. Several AVT agonists, including hydrin 2, oxytocin (OXT), arginine vasopressin (AVP), Lys-conopressin G, and mesotocin (MT), were able to mimic the stimulatory effect of AVT on steroid secretion, but AVT was by far the most potent stimulator of steroidogenesis. In the series of analogs studied, the order of potency was: AVT greater than hydrin 2 greater than OXT greater than AVP greater than Lys-conopressin G greater than MT greater than [deamino-Cys1,D-Arg8]AVP greater than [d(CH2)5,Tyr(OMe)2] AVP. The effect of AVT (5 x 10(-10) M) was totally blocked by both the antidiuretic V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP (10(-6) M) and the oxytocinergic antagonist [d(CH2)5,Tyr(OMe)2,Orn8]AVT (10(-6) M); the V2 antagonist was approximately twice as potent as the OXT antagonist. In contrast, the V1 antagonist 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-AVP (10(-6) M) did not affect the response of the interrenal tissue to AVT. Indomethacin (5 microM), a cyclooxygenase inhibitor, induced a dramatic decrease in the spontaneous secretion of corticosteroids, but did not impair the stimulatory effect of AVT (5 x 10(-9) M) on corticosterone and aldosterone secretion. In addition, AVT did not stimulate the production of prostaglandin E2, suggesting that prostaglandins are not involved in the mechanism of action of AVT. Concurrently, AVT did not modify cAMP production by frog adrenal slices. In contrast, AVT induced both an increase in inositolphosphate production and a reduction of membrane phospholipid content. We conclude that in the frog adrenal gland, the stimulatory effect of AVT on steroid secretion is mediated through activation of receptors related to the mammalian V2 and/or OXT receptors, which are positively coupled to phosphoinositide-specific phospholipase C.
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PMID:Pharmacological characterization of vasotocin stimulation of phosphoinositide turnover in frog adrenal gland. 130 45

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.
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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

Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression.
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PMID:Uterine secretion of prostaglandin F2 alpha in the ewe: regulation at the cellular level by ovarian hormones and the conceptus. 143 63

Studies were performed to identify the receptor that mediates AVP-stimulated phosphoinositide (PI) hydrolysis in cultured rat inner medullary collecting tubule (RIMCT) cells. While the selective V1 receptor agonist [Ho1, Phe2, Orn8] VT has no effect on inositol trisphosphate (IP3) production over the range of 10(-13)-10(-7) M, the selective V2 receptor agonist VDAVP stimulates IP3 production in dose-dependent fashion. Oxytocin stimulates IP3 production in dose-dependent fashion as well. AVP-stimulated phospholipase C activity is not inhibited by the V1 receptor antagonist d(CH2)5Tyr(Me)AVP(10(-7) M) but is eliminated by the V2 receptor antagonist d(CH2)5DTyr(Et)VAVP (10(-7) M). Similarly, the response to oxytocin is eliminated by the V2 receptor antagonist. The selective oxytocin receptor agonist [Thr4, Gly7] oxytocin does not stimulate cAMP production in RIMCT cells but does promote PI hydrolysis. The selective oxytocin receptor antagonist desGlyNH2d(CH2)5[Tyr(Me)-Thr4]OVT (10(-7) M) does not inhibit AVP-stimulated cAMP production but eliminates IP3 production in response to AVP or the V2 receptor agonist VDAVP. These studies demonstrate that AVP or a V2 receptor agonist stimulate PI hydrolysis in cultured RIMCT cells via occupancy of the oxytocin receptor.
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PMID:Vasopressin-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting duct cells is mediated by the oxytocin receptor. 164 53

Progesterone and estradiol interact to regulate secretion of prostaglandin (PG) F2 alpha from the ovine endometrium in response to oxytocin. Two experiments were conducted to determine if these effects were due to changes in activity of phospholipase C or in the second messenger responsive pathways that regulate production of PGF2 alpha. In both experiments, ovariectomized ewes were assigned to one of four treatment groups (control, estradiol, progesterone, progesterone and estradiol). Steroids were administered, in vivo, to mimic the changes that occur during the estrous cycle. On Day 16 of steroid treatment, endometrial tissue was collected and incubated, in vitro, to measure activity of phospholipase C and release of PGF2 alpha. Treatment with progesterone, in vivo, enhanced basal and oxytocin-induced activity of phospholipase C and release of PGF2 alpha, in vitro. Estradiol suppressed oxytocin-induced activity of phospholipase C, both in the presence and absence of progesterone. In contrast to its effects on phospholipase C, estradiol inhibited basal and oxytocin-induced release of PGF2 alpha when administered alone, but not when administered with progesterone. Steroids had similar effects on the release of PGF2 alpha induced by phorbol 12-myristate 13-acetate and A23187. It was concluded that progesterone and estradiol regulate endometrial release of PGF2 alpha by affecting both the activity of phospholipase C and its associated second messenger responsive pathways that may regulate production of PGF2 alpha.
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PMID:Activity of phospholipase C and release of prostaglandin F2 alpha by endometrial tissue from ovariectomized ewes receiving progesterone and estradiol. 201 59

The effects of phorbol 12, 13-dibutyrate (PDB) on mechanical activity in the pregnant rat uterus were investigated in isolated strips. In Ca(++)-containing solution, PDB (2.5 x 10(-8) to 10(-6) M) increased in a concentration-dependent manner the amplitude of the electrically induced contraction, but had no effect on the resting tension. PDB (10(-7) M) had a dual action, stimulatory then inhibitory, on contractions evoked by K(+)-rich (40 mM K+) solution or oxytocin. The inhibitory effect appeared more rapidly and the percentage of inhibition was increased for 10(-6) M PDB, which in addition abolished completely oxytocin-induced contraction after 20 min of application. PDB also reduced the amplitude of transient contraction evoked by oxytocin in Ca(++)-free solution. In saponin-skinned strips, 10(-7) M PDB increased the contraction induced by pCa ranging from 7 to 6, whereas 10(-6) M PDB reduced all Ca(++)-activated contractions from pCa = 7 to pCa = 5. PDB had no significant effect on the Ca(++)-uptake and the Ca(++)-release mechanisms of the intracellular Ca(++)-store. All of the effects of PDB were antagonized by the addition of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (2 x 10(-5) M). In addition, the inactive phorbol 13,20-diacetate (10(-8) to 10(-6) M) had no effect on the mechanical activity in uterus. These results suggest the existence of different sites of action of PDB in rat uterus, via the activation of protein kinase C: 1) contractile machinery; 2) potential-dependent Ca channels; and 3) phospholipase C.
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PMID:An analysis of the action of phorbol 12, 13-dibutyrate on mechanical activity in rat uterine smooth muscle. 221 48

Phosphoinositide-specific phospholipase C (PI-PLC) activity was determined in homogenates of adipocytes treated with maximal concentrations of insulin. PI-PLC activity measured using exogenous [3H]phosphatidylinositol [( 3H]PI) and exogenous [3H]phosphatidylinositol 4,5-bisphosphate [( 3H]PIP2) was not altered by prior exposure of adipocytes to insulin. It was possible to see oxytocin-induced breakdown of phosphoinositides but no effect of insulin was seen in intact adipocytes.
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PMID:Insulin does not activate a phosphoinositide-specific phospholipase C in adipocytes. 255 35

The synthesis of new radiolabelled compounds and the evolution of the techniques designed to study the hormonal receptors allow a better understanding of their properties. Three types of vasopressin receptors have been described: the V1a receptor of liver and blood vessels, the V1b receptor of hypophysis and the V2 receptor of kidney. Such a classification was based on two criteria: The structure of the binding site and the nature of the second messenger produced. The V2 receptor coupled positively to adenylate cyclase regulates the water reabsorption via the increase of intracellular cyclic AMP. The V1a and V1b receptors involved in glycogenolysis, contraction and probably neurotransmission mobilize intracellular calcium via a positive coupling to phospholipase C. These two receptors exhibit different recognition patterns for vasopressin analogues. In mammals, the oxytocin receptors are mainly involved in myometrial contraction and lactation. Their characterization are generally difficult since they also interact with vasopressin and are sometimes colocated with vasopressin receptors. As for V1 receptor, they are coupled to phospholipase C and mobilized intracellular calcium. The receptors of angiotensin II regulate the blood pressure by different mechanisms. They are coupled to at least two transduction mechanisms (positive coupling to phospholipase C and negative coupling to adenylate cyclase). Electrophysiological data seems to indicate that such receptor may also control a calcium channel. Yet different molecules (cAMP, calcium, inositol phosphates, diacyl-glycerol) trigger the hormonal effect of angiotensin II inside the cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Vasopressin, oxytocin and angiotensin receptors in mammals]. 269 9


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