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

The myometrial contractile responses to synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor, PAF) and to oxytocin were evaluated in vitro on uterine (lower segment) strips obtained from pregnant women at term (39th week), undergoing elective cesarean section. Contractility was measured isometrically in an isolated organ bath using a superfusion technique. PAF in a concentration range between 5 and 100 nM as well as oxytocin (0.1-10 mU/ml) induced a dose-dependent contraction which could be categorized in two patterns, depending on whether spontaneous activity was present. In resting strips, oxytocin induced a prompt (0.5-1 min) development of active tension, followed by a prolonged (6-18 min), slow contraction and a final relaxation. However, at variance with oxytocin, PAF-induced contractions were rhythmic (3-8/hr), and characterized by a prompt (0.5-2 min) development of tension, followed by a brief (0.5-2 min) plateau, and a final, rapid relaxation. In spontaneously active strips, both stimuli induced a marked potentiation of the contractile activity. PAF response was dependent on both cyclooxygenase- and lipoxygenase-derived products as inferred from the abrogating effects of indomethacin and FPL 55712. A receptor-mediated mechanism of action was inferred from the occurrence of specific desensitization to PAF (but not to oxytocin), and from the blocking effect of CV 3988, a specific PAF receptor antagonist. The present study indicates that PAF stimulates the contraction of human myometrium in vitro and suggests that this mediator may have a role in labor.
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PMID:Platelet-activating factor contracts human myometrium in vitro. 379 21

Platelet-activating factor (PAF) evoked myometrial contractions in two different patterns, depending on whether spontaneous activity was present. In spontaneously active myometrial strips (58%), both PAF and oxytocin enhanced the amplitude of myometrial contractions. In quiescent myometrial strips, PAF induced contractions characterized by a prompt development of tension, a plateau, and a final, rapid relaxation. In 54% of these strips, PAF-induced contraction was followed by rhythmic activity. PAF contractile response was dependent upon the concentration (0.1-100 nM); the minimal effective concentration of PAF was 0.1 nM and the EC50 was 1 nM. The response to oxytocin (0.01-10 mU/ml), assumed as reference stimulus, was characterized by a prompt development of tension, which was followed by a sustained, slow contraction and relaxation. PAF response was almost completely dependent on cyclooxygenase and partially on lipoxygenase pathways, as inferred from studies with indomethacin and FPL 55712, respectively. A receptor mediated mechanism of PAF action was suggested by specific desensitization of the myometrium to a second challenge with an equimolar concentration of PAF (but not with oxytocin) and the blocking effect of CV 3988, a specific PAF receptor antagonist.
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PMID:In vitro contractile effect of platelet-activating factor on guinea-pig myometrium. 379 92

Normal human endometrium (classified by histology and date after last menstrual period) was cultured for 72h, and the output of prostaglandin F2 alpha and 6-oxo-prostaglandin F1 alpha detected by radioimmunoassay. Hormones/stimuli were added to the culture during the second day of culture for 5h and 19h periods. The output of prostaglandin F2 alpha from cultured endometrium was significantly higher (p less than 0.05) at the beginning (d4-8) and end (d25-30) of the menstrual cycle, compared to mid-cycle (d13-24) endometrium. Significantly more prostaglandin F2 alpha was released from proliferative than from secretory phase endometrium (p less than 0.02). Prostaglandin F2 alpha release was rapidly stimulated by sodium arachidonate (20-300 micrograms/ml), and by calcium ionophore A23187 (5 micrograms/ml) at an extracellular calcium ion concentration of 1.8mM. The ionophore stimulation was greater in mid-cycle endometrium than in endometrium from the beginning or the end of the menstrual cycle. Estradiol-17 beta (10 ng/ml) gradually increased the output of prostaglandin F2 alpha from secretory phase endometrium, and this stimulation was observed in the post-incubation period after hormone had been removed from the incubation medium. Oxytocin (1 X 10(-5) U/ml caused a more rapid stimulation of prostaglandin F2 alpha output from secretory phase tissue (p less than 0.05 during the first 5h incubation period with hormone). Oxytocin (1 X 10(-5) U/ml) and estradiol (10ng/ml) together significantly stimulated prostaglandin F2 alpha production by proliferative as well as secretory phase endometria. A high dose of hydrocortisone (100 micrograms/ml) inhibited the output of prostaglandin F2 alpha from proliferative and secretory phase endometrium and also from ionophore-stimulated endometrium. However, this dose of hydrocortisone did not inhibit the synthesis of prostaglandin F2 alpha from exogenous arachidonic acid, or the estradiol-induced increase in prostaglandin F2 alpha production. Co-culture of endometrium with myometrium did not modify the output of prostaglandin F2 alpha or of 6-oxo-prostaglandin F1 alpha from cultured tissues. These experiments suggest that arachidonic acid supply to the cyclooxygenase enzyme may vary during the menstrual cycle; and indicate a gradual increase in prostaglandin synthesising capacity in response to estrogen, more rapid control via oxytocin, and an interaction between estrogen and oxytocin to modulate prostaglandin F2 alpha synthesis in human endometrium.
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PMID:The effect of oxytocin, estrogen, calcium ionophore A23187 and hydrocortisone on prostaglandin F2 alpha and 6-oxo-prostaglandin F1 alpha production by cultured human endometrial and myometrial explants. 642 64

1. The effects of estrogens estradiol (E2, 10(-6)-10(-4) M) and diethylstilbestrol (DES, 10(-6)-10(-4) M) and the antiestrogens nafoxidine (N, 10(-6)-10(-4) M), tamoxifen (T, 10(-6)-6 x 10(-4) M), tamoxifen ethyl bromide (TEB, 10(-4) M) and ICI 164,384 (ICI, 10(-5) M) on tonic contractions induced by oxytocin (2 x 10(-8) M) or vanadate (3 x 10(-4) M) in rat uterus incubated in calcium-free EDTA treated solution have been assayed. 2. E2 and DES relaxed the tonic contraction induced by oxytocin in a dose dependent way (EC50: 1.11 +/- 0.01 x 10(-4) M and 1.5 +/- 0.07 x 10(-5) M). The vanadate-induced contraction only was relaxed with DES (57.62 +/- 2.38% at 10(-3) M). 3. The effect of DES on oxytocin contraction was unmodified by the protein synthesis inhibitor cycloheximide (10 micrograms/ml) and by the cyclooxygenase inhibitor indomethacin (3 x 10(-6) M), but enhanced by the intracellular calcium release inhibitor TMB-8 (10(-5) M). The antiestrogen tamoxifen (3 x 10(-5) M) promotes the relaxing effect of DES. 4. The antiestrogens N, and T, but not ICI, relaxed the oxytocin-induced contraction (EC50: 4.51 +/- 0.43 x 10(-5) M and 2.27 +/- 0.05 x 10(-4) M). TEB (10(-4) M) produces a relaxation of 74.5 +/- 2.11%. The vanadate contraction is also relaxed by T (EC50: 6.03 +/- 0.04 x 10(-4) M). 5. The effect of T on oxytocin contraction was unmodified with cycloheximide or TMB-8 but decreased with indomethacin.
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PMID:Estrogen and antiestrogen non-genomic effect in rat uterus contraction in calcium-free solution. 848 24

The use of prostaglandins in obstetrics has undergone a rapid evolution since their discovery in the early 1970s. It appears certain now that, at least in some cases, prostaglandins are important mediators of uterine activity. Indeed, a much stronger case can be made for the role of prostaglandins in labor than can be made for oxytocin. The pivotal role of prostaglandins in contraction of the smooth muscle of the uterus and the biophysical changes associated with cervical ripening, however, point to a major problem with their clinical use. Prostaglandins are produced by almost every tissue in the body and serve as important messengers or effectors in a wide variety of functions. Attempts to inhibit the production of prostaglandins to produce a reduction in myometrial contractility are limited by the important role of prostaglandins in maintenance of fetal ductal flow and renal blood flow. Similarly, administration of prostaglandins for the purpose of inducing labor or ripening an unfavorable cervix is tempered by the effects of these agents in other systems, including the gut and brain. Significant advances, however, have been made in the application of prostaglandins to common clinical problems in obstetrics. Of the multitude of products derived from the actions of cyclooxygenase on arachidonic acid, the most important for labor, delivery, and the postpartum period are the F and E series prostaglandins. Unlike oxytocin which requires an induction of receptors that does not usually occur until the later part of pregnancy, prostaglandins receptors always are present in myometrial tissue. This allows for the use of prostaglandins in usual doses throughout pregnancy. Although both F and E series prostaglandins result in uterine contractions, E series prostaglandins are relatively more uteroselective and are clearly superior to F series prostaglandins in producing cervical ripening. Modification of the naturally occurring prostaglandins by blocking the sites that are affected during their usual rapid metabolism, results in products with much longer durations of action, efficacy at much lower concentrations, and a potential for significant savings in cost. We are now able to manage efficiently problems such as intrauterine fetal death and intractable hemorrhage from postpartum uterine atony that often resulted in a surgical procedure prior to the availability of prostaglandin. We can continue to explore the potential of these agents in helping to solve the most difficult problems faced by the obstetrician.
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PMID:The role of prostaglandins in labor and delivery. 866 68

There is substantial experimental evidence suggesting that oxytocin has a role in luteolysis in ruminates. Endogenous pulses of uterine prostaglandin (PG) F2 alpha occur synchronously with pulses of oxytocin during luteolysis; leading us to propose a possible feedback loop between uterine PGF2 alpha and luteal oxytocin. In rates, the mechanism whereby oxytocin acts has not been well elucidated. In the present report, the effects of an oxytocin receptor antagonist in pseudopregnant rats were investigated. Pseudopregnancy was induced in immature female rats by gonadotrophin treatment; this resulted in the formation of corpus luteum that remained functional for 9 +/- 1 days. The pseudopregnant rats were assigned to one of the following four groups. In the first group the relationship between the release of ovarian and uterine PGF2 alpha was tested. We also studied the serum progesterone during the pseudopregnancy. We found that PGF2 alpha released into the incubation medium from ovaries of pseudopregnant rats increased (p < 0.05) and was maximal on day 9 of pseudopregnancy. This concentration remained high until day 10 of pseudopregnancy and then decreased. The PGF2 alpha released from the uterus to the incubation medium rose (p < 0.05) on day 8 of pseudopregnancy and reached the peak value on day 10. the serum progesterone was increased (p < 0.001) on day 2 pseudopregnancy and was greater on day 5 (p < 0.001). The second and third group received a specific oxytocin receptor antagonist (1-deamino-2-O-methyltyrosine) in two different concentrations (0.05 or 0.2 mumol/l before the peak of PG release. Both doses employed decreased (p < 0.001) the release into the incubating medium of PGF2 alpha from ovaries and uterus. Indeed, after the treatment, the progesterone levels were higher (p < 0.001) than control on day 10 of pseudopregnancy. In the fourth group, a potent inhibitor of cyclooxygenase activity was administered on day 8 of pseudopregnancy into the ovarian bursa. The serum progesterone levels increased (p < 0.01) compared to control suggesting a possible role of ovarian PG in the luteolytic phase of the corpus luteum regression. Thus, our findings show that oxytocin is luteolytic in pseudopregnant rats and this action is mediated by oxytocin receptors, as it was blocked by a specific oxytocin receptor antagonist.
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PMID:Effect of an oxytocin receptor antagonist on ovarian and uterine synthesis and release of prostaglandin F2 alpha in pseudopregnant rats. 884 36

The febrile and neuroendocrine responses to circulating endotoxin are effected, at least in part, by a central action of prostaglandins with interleukins serving as intermediaries. Data from rodents suggest that prostaglandin and interleukin (IL-1 beta) synthesis in response to endotoxin challenge may occur within the circumventricular organs of the brain, especially the choroid plexus; the present study investigated this possibility using the sheep as an experimental model. A pyretic dose of bacterial endotoxin (40 micrograms lipopolysaccharide) was given intravenously to sheep (n = 5) and the effect on gene expression in the choroid plexus after a 40 min interval was compared with that observed in vehicle-treated animals (n = 5) using in situ hybridisation histochemistry. Evidence of activational and synthetic events following endotoxin administration was provided by significant increases in c-fos (P < 0.05) and IL-1 beta (P < 0.01) mRNA expression. Constitutive cyclooxygenase (cox-1 mRNA) and inducible cyclooxygenase (cox-2 mRNA) synthesis were unchanged. The investigation also sought to provide evidence for endotoxin effects on neuroendocrine activity in this species by examining changes in hypothalamic gene expression. The results showed that c-fos mRNA increased in the paraventricular (P < 0.01) and supraoptic (P < 0.05) nuclei and that CRH mRNA was upregulated in the paraventricular nucleus (P < 0.001). However, in agreement with previous work, there was no change in vasopressin gene expression although oxytocin mRNA was enhanced throughout the paraventricular nucleus (P < 0.05). These findings suggest the following: (1) possible involvement of the choroid plexus in the response of sheep to immunological challenge: (2) endotoxin-induced changes in gene expression in the ovine hypothalamus similar in those caused by other stressors: and (3) possible changes in oxytocin synthesis concomitant with fever in the sheep.
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PMID:Bacterial endotoxin-induced gene expression in the choroid plexus and paraventricular and supraoptic hypothalamic nuclei of the sheep. 903 17

Neurons containing neural nitric oxide synthase (nNOS) are found in various locations in the hypothalamus and, in particular, in the paraventricular and supraoptic nuclei with axons which project to the median eminence and extend into the neural lobe where the highest concentrations of NOS are found in the rat. Furthermore, nNOS is also located in folliculostellate cells and LH gonadotropes in the anterior pituitary gland. To define the role of NO in the release of hypothalamic peptides and pituitary hormones, we injected an inhibitor of NOS, Ng-monomethyl-L-arginine (NMMA) or a releasor of NO, nitroprusside (NP) into the third ventricle (3V) of conscious castrate rats and determined the effect on the release of various pituitary hormones. In vitro, we incubated medial basal hypothalamic (MBH) fragments and studied inhibitors of NO synthase and also releasors of NO. The results indicate that NOergic neurons play an important role in stimulating the release of corticotrophin-releasing hormone (CRH), luteinizing hormone releasing-hormone (LHRH), prolactin-RH's, particularly oxytocin, growth hormone-RH (GHRH) and somatostatin, but not FSH-releasing factor from the hypothalamus. NO stimulates the release of LHRH, which induces sexual behavior, and causes release of LH from the pituitary gland. The intrahypothalamic pathway by which NO controls LHRH release is as follows: glutamergic neurons synapse with noradrenergic terminals in the MBH which release nonepinephrine (NE) that acts on alpha 1 receptors on the NOergic neuron to increase intracellular free Ca++ which combines with calmodulin to activate NOS. The NOS diffuses to the LHRH terminal and activates guanylate cyclase (GC), cyclooxygenase and lipoxygenase causing release of LHRH via release of cyclic GMP, PGE2 and leukotrienes, respectively. Alcohol and cytokines can block LHRH release by blocking the activation of cyclooxygenase and lipoxygenase without interfering with the activation of GC. GABA also blocks the response of the LHRH neurons to NO and recent experiments indicate that granulocyte macrophage colony-stimulating factor (GMCSF) blocks the response of the LHRH neuron to NP by activation of GABA neurons since the blockade can be reversed by the competitive inhibitor of GABAa receptors, bicuculine.
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PMID:The role of nitric oxide (NO) in control of hypothalamic-pituitary function. 939 93

Prostaglandin E2 (PGE2) can cause softening of the bovine cervix at oestrus when receptors for oxytocin (OT) are maximally present, indicating a relationship between OT and PGE2 production. It was therefore determined whether OT can stimulate prostaglandin synthesis or induce cyclooxygenase expression in cervical external os segments obtained from pre-oestrous-oestrous cows. Tissues were minced and incubated (50-100 mg mL[-1] 6 h[-1]) in the presence of OT (10 ng mL[-1]), progesterone (P4) (5 ng mL[-1]) and/or indomethacin (5 microg mL[-1]). It was found that OT stimulated basal PGE2 (7.79+/-1.22 ng 100 mg[-1], mean+/-s.e.m.; n = 6) in external os segments from pre-oestrous-oestrous cows (P < 0.03), whereas P4 and indomethacin inhibited basal and OT-stimulated PGE2 production (P < 0.05). Basal prostaglandin F2alpha (PGF2alpha) production was minimal (<1 ng 100 mg[-1]) and OT had no effect on its production. Expression of cyclooxygenase was measured by Western blot analysis following incubation of the tissue (100 mg 1.5 mL[-1] 3 h[-1]) in the presence of OT (10 ng mL[-1]) and in the presence of P4 (5 ng mL[-1]). It was found that OT stimulated the induction of cyclooxygenase II (79+/-10%; n = 7, P < 0.05). In contrast, P4 inhibited the basal expression of this enzyme (-40+/-5%, n = 7, P < 0.05) in the presence or absence of OT. It is concluded that, in vitro, OT stimulates PGE2 synthesis by the bovine cervix at oestrus and that this effect is mediated by cyclooxygenase.
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PMID:Regulation of bovine cervical secretion of prostaglandins and synthesis of cyclooxygenase by oxytocin. 941 82

Although melatonin has been reported to influence neurohypophysial hormone release, no binding has been demonstrated in the neurohypophysial system, suggesting melatonin could affect afferent inputs. The effect of neurotransmitter receptor antagonists on the inhibitory effect of melatonin on neurohypophysial hormone release from the rat hypothalamus in vitro was therefore determined. The agents employed were atropine, a muscarinic cholinergic antagonist; mecamylamine, a nicotinic cholinergic antagonist; atenolol, a beta-adrenergic antagonist; phentolamine, a nonselective alpha-adrenergic antagonist; prazosin, a selective alpha-adrenergic antagonist; haloperidol, a dopaminergic antagonist; naloxone, an opioid antagonist; and ibuprofen, a cyclooxygenase inhibitor. Rat hypothalami were incubated in either medium alone or medium containing melatonin or melatonin and antagonist, and hormone release determined. Melatonin (43 nM) significantly inhibited (p < 0.05) vasopressin and oxytocin release. Inhibition was still observed in the presence of atenolol, phentolamine, and naloxone, suggesting that neither adrenergic nor opioid pathways contribute to the response. The inhibitory effect of melatonin on vasopressin and oxytocin release was abolished (p < 0.05) in the presence of atropine (10[-8] M), mecylamine (10[-6] and 10[-4] M), ibuprofen (10[-4] M) and haloperidol (10[-6] and 10[-5] M). The melatonin-induced inhibition of oxytocin release was also attenuated in the presence of prazosin (10[-8] and 10[-6] M). This study suggests that melatonin may influence neurohypophysial hormone release through modulation of afferent pathways mediated by acetylcholine, dopamine, and/or prostaglandin.
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PMID:Mechanisms of melatonin inhibition of neurohypophysial hormone release from the rat hypothalamus in vitro. 943 2


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