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

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

We have examined the effects of arachidonic acid (AA) and some of its metabolites on progesterone (P4) and oxytocin (OT) release by corpora lutea obtained from Holstein heifers at day 8 of the estrous cycle (Day 0 = estrus). The luteal cells were dispersed with collagenase and small and large cells were separated by unit gravity sedimentation and flow cytometry. After an 18-hr preincubation period, the cells were incubated in the presence of various treatments for 1 hr, followed by a 23-hr incubation period with no treatment. OT was secreted by the large, but not by the small, luteal cells into the incubation medium. AA elicited a significant (P less than 0.05) release of OT from the large cells and P4 from both the large and small cells within 1 hr of incubation, having a specific effect at a concentration of 10 microM. Larger doses (25 and 100 microM) of AA adversely affected the cell viability. Phospholipases A2 (0.5 unit/ml) and C (0.05 unit/ml) and calcium ionophore A23187 (0.1 microM) stimulated OT release from the large cells to the same extent as AA (10 microM). Inhibition of the AA cyclooxygenase metabolic pathway by indomethacin did not affect AA-induced release of OT and P4, although exogenous prostaglandins F2 alpha and I2 (5-25 ng/ml) stimulated the release of OT. Lipoxygenase products of AA (hydroxyeicosatetraenoic acid and leukotrienes; 25 ng/ml) also stimulated OT release. Inhibition of the lipoxygenase metabolic pathway by nordihydroguaiaretic acid abolished AA-induced release of both OT and P4. These results suggest that intracellular accumulation of free AA may modulate secretory functions in the bovine corpora lutea, including OT and P4 release.
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PMID:Role of arachidonic acid and its metabolites in the regulation of progesterone and oxytocin release from the bovine corpus luteum. 152 4

In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of prostaglandin F2 alpha (PGF2 alpha) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2 alpha secretion from the uterus. Uterine PGF2 alpha stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2 alpha from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2 alpha at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2 alpha observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2 alpha normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2 alpha occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2 alpha secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2 alpha. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2 alpha is secreted only at the appropriate time to induce luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of uterine secretion of prostaglandin F2 alpha during luteolysis in ruminants. 175 3

We have recently demonstrated that corticotropin releasing hormone (CRH) potentiates the contractile response to oxytocin of human gestational myometrium, using a high flow microsuperfusion system and electrical field stimulation. We now report this potentiation to be equivalent to that of 1 nM prostaglandin F2 alpha (PGF2 alpha), while 10 nM PGF2 alpha did not potentiate the response to oxytocin. Prostaglandin E2 (PGE2) also showed no augmentation of the contraction force of the myometrium in response to oxytocin. The CRH potentiated response was inhibited by the lipoxygenase and cyclooxygenase inhibitor BW755C (1 microM) and by indomethacin (0.1 microM), but not by the lipoxygenase inhibitor BW4C (1 microM). Measurements of prostaglandins in the superfusate showed no significant trends. It is concluded that the potentiation of contraction force to oxytocin by CRH is dependent on prostaglandins, probably PGF2 alpha and that leukotrienes, generated via the lipoxygenase pathway are not involved.
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PMID:Role of prostaglandins and leukotrienes in the synergistic effect of oxytocin and corticotropin-releasing hormone (CRH) on the contraction force in human gestational myometrium. 177 36

Two experiments were conducted to determine if intrauterine infusion of nordihydroguaiaretic acid, a lipoxygenase pathway inhibitor, would delay luteolysis (Experiment 1) and inhibit oxytocin-induced release of prostaglandin F2 alpha (as measured by the stable prostaglandin F2 alpha metabolite, 15-keto-13,14-dihydroprostaglandin F2 alpha) in plasma on d 16 (d 0 = estrus) of the estrous cycle (Experiment 2). Nordihydroguaiaretic acid (20 mg) or saline was infused twice daily into the uterus on d 14 to 23 (Experiment 1) or d 14 to 20 (Experiment 2) postestrus, respectively. In Experiment 1 and 2, mean concentration of progesterone was higher and luteolysis was delayed in nordihydroguaiaretic acid-infused heifers compared with saline-infused heifers. In Experiment 2, saline or oxytocin (100 IU, i.v.) was injected into each heifer on d 16 postestrus to stimulate the release of prostaglandin F2 alpha from the uterus. Mean concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha increased within 1.5 h postinjection in heifers infused with saline, whereas concentration of 15-keto-13,14-dihydroprostaglandin F2 alpha in nordihydroguaiaretic acid-infused heifers did not increase within the same time period. Thus, nordihydroguaiaretic acid may inhibit both the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism and therefore delay luteolysis.
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PMID:Effect of nordihydroguaiaretic acid on luteal phase length and oxytocin-induced release of prostaglandin F2 alpha in heifers. 225 84

Indomethacin and substance BW-755C in experiments on isolated myometrium striae of pregnant white rats exert an inhibiting effect on the contractile uterus function due to inhibition of cyclooxygenase or lipoxygenase ways of the arachidonic acid transformation. Prostaglandin F2 alpha is sensitive to functioning of the cyclooxygenase and lipoxygenase ways of the arachidonic acid transformation, while oxytocin--only lipoxygenase one. Conclusions rest on results from multiparametric analysis of the contractile uterus function suggested by authors and confirmed by the pattern recognition method--the Karunen-Loev orthogonal decomposition.
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PMID:[Comparative evaluation of the action of prostanoid inhibitors on uterine contractile function]. 250 61

We measure oxytocin (OT) responsiveness and prostaglandins (PGs) synthesis in uteri of 19, 20, 21 and 22-day pregnant and 2-day postpartum rats to determine whether the enhanced OT sensitivity and PG synthesis in the parturient uterus is the result of a higher cyclooxygenase activity. We also investigated the effects of suppression of PG synthesis on OT responsiveness and OT receptor in 22-day and 23-day pregnant rats. PG productions (PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 in microsomal fractions were quantitated by radio- immunoassays (RIAs). OT receptor concentrations were measured in plasma membrane fractions by radioligand-receptor binding assays. Naproxen sodium was used to inhibit endogenous PG synthesis. We found a close temporal relationship between enhanced OT responsiveness and increased uterine PGE2 alpha synthesis, but no significant difference in cyclooxygenase activities among the microsomes prepared from uteri of different gestational ages. Suppression of PG synthesis attenuated OT responsiveness and markedly reduced OT binding sites, from 242 to 78 fmol/mg protein. There was no change in the binding affinity. These findings suggest that PG stimulates OT receptor formation which leads to enhanced OT responsiveness. The increase in PG production is not mediated by a higher cyclooxygenase activity.
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PMID:Enhanced prostaglandin synthesis in the parturient rat uterus and its effects on myometrial oxytocin receptor concentrations. 283 92

We examined the relation between increased uterine oxytocin receptor concentration and increased in vivo sensitivity of the rabbit uterus to oxytocin at the end of gestation. We determined oxytocin receptor concentrations in myometrium and decidua on different days near term of gestation and postpartum. We also examined the in vitro contractile response to oxytocin on days 30 and 5 days postpartum, when the uterus is unresponsive in vivo, and on day 31 (term), when the uterus is exquisitely sensitive to this hormone in vivo. In addition, we tested the role of endogenous eicosanoids and decidual oxytocin receptors in the myometrial contractile response to oxytocin by examining the contractile response in the presence of the cyclooxygenase/lipoxygenase inhibitor sodium meclofenamate or in muscle strips from which the decidua had been removed by scraping. The concentration of specific binding sites for [3H]oxytocin in myometrial and also decidual membrane preparations was determined. We demonstrate that contractile sensitivity to oxytocin increases at least 4-fold between days 30 and 31 (term) of gestation, and this is accompanied by a nearly 10-fold increase in the concentration of oxytocin-binding sites in both decidua and myometrium. The lesser sensitivity to oxytocin on day 30 was, however, only apparent in the presence of meclofenamate, which suggests that endogenous eicosanoids contribute to the preterm response to oxytocin measured in vitro. The maximal response to oxytocin (integrated area) increased 2-fold between day 30 and term. Thus, an increase in both sensitivity and maximal response to oxytocin could be demonstrated at term in vitro. Five days after parturition, maximal response and uterine sensitivity measured in the presence of meclofenamate had returned to those of the preterm uterus, and the concentration of oxytocin-binding sites had declined. In contrast, sensitivity and maximal response to the cholinergic agonist carbamylcholine declined between day 30 and term. These results support a highly regulated physiological role for oxytocin in parturition which depends primarily on changes in receptor concentration.
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PMID:Rabbit uterine oxytocin receptors and in vitro contractile response: abrupt changes at term and the role of eicosanoids. 301 54

Oxytocin (50-750 nM) contracted the isolated testicular capsule of the rat. Mepacrine, a phospholipase A2 inhibitor (3 X 10(-5) M) and the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) M) inhibited this response whereas the cyclooxygenase inhibitor, diclofenac sodium (10(-5) M), and the thromboxane synthetase inhibitor imidazole (10(-5) M) did not. It appears that metabolites of arachidonic acid dependent on lipoxygenase are involved in the contractile response of the rat testicular capsule to oxytocin.
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PMID:Influence of some inhibitors of arachidonic acid metabolism on oxytocin contractions in the isolated testicular capsule of the rat. 310 57

Current and emerging concepts on regulation of bovine corpus luteum function by various metabolites of arachidonic acid are reviewed. A series of experiments are presented which support the concept that prostacyclin (PGI2), a metabolite of arachidonic acid via the cyclooxygenase pathway, plays a luteotropic role, and that products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5-hydroxyeicosatetraenoic acid (5-HETE), play a luteolytic role in the function of the bovine corpus luteum (CL). These ideas are supported by the following findings: injection of PGI2 directly into CL at mid-cycle produced a prolonged increase in peripheral plasma concentrations of progesterone; PGI2 stimulated synthesis of progesterone by dispersed luteal cells; synthesis of PGI2 by luteal cells was greatest during the period of early CL development (d 5 and 10), and diminished as the CL aged unless pregnancy ensued, causing a maintenance of the CL and synthesis of PGI2; administration of indomethacin, a blocker of synthesis of prostaglandin by the cyclooxygenase pathway, twice daily on d 4 to 6 of the estrous cycle inhibited CL development and caused a reduction in cycle length, suggesting the presence of a luteotropic prostaglandin; oxytocin administration twice daily on d 4 through 6 inhibited CL development and was accompanied by a 50% reduction in luteal synthesis of PGI2 by CL collected on d 7; large quantities of 5-HETE were found in luteal tissue; the addition of 5-HETE to dispersed luteal cells inhibited synthesis of progesterone and PGI2, while production of PGF2 alpha was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of luteal prostaglandins in the control of bovine corpus luteum functions. 353 77


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