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

Platelet function has been studied during intravenous, intraamniotic, and extraamniotic administration of prostaglandin F2alpha (PgF2alpha) for termination of missed abortion and missed labor, for therapeutic abortion, and for induction of term labor. The controls received oxytocin i.v. (missed labor and term labor). Our investigations have shown that there was a normalization of the increased spontaneous platelet aggregation and a significant reduction of ADP- and collagen-induced platelet aggregation in the groups given PgF2alpha i.v. The desaggregation in these groups was increased. The other groups given PgF2alpha showed no significant changes in platelet function. Inducing labor by oxytocin we found a tendency to increased platelet aggregation and decreased desaggregation. The clinical importance of these findings and the consequences for hemostasis are discussed.
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PMID:Studies on platelet function during different modes of administration of PgF2alpha in obstetrics and gynecology. 58 Oct 52

This study examines platelet aggregation in 17 women having labor induced by low amniotomy and oral administration of PGE2 (prostaglandin E2). Venous blood samples were collected before and after induction of labor, the 1st sample acting as control for the 2nd. Born's method (1962) was used to study platelet aggregation. Aggregation studies were done on both samples, between 60 and 90 minutes after venepuncture. Similar experimental procedure was carried out in 3 patients who had spontaneous onset of labor without the administration of oral PGE2 or intravenous oxytocin. The extent of primary and secondary ADP-induced aggregation was measured as the percentage increase in light transmittance. Student's t test and the Mann Whitney U test were used for statistical analyses. Minimum final ADP concentration needed to elicit the characteristic biphasic aggregation response was 0.5 mcg/ml in 7 patients, and 1.0 mcg/ml in the other 10 patients. Significant inhibition of primary aggregation after oral PGE2 administration occurred at a dose level of 0.5 mcg/ml of ADP. Those who had ADP concentration of 1.0 mcg/ml did not exhibit significant inhibition of primary aggregation. At both levels, no significant difference was observed in the amount of PGE2 ingested up to the time of venepuncture (P0.2). Platelets from the 3 control patients did not exhibit any differences in either primary or secondary ADP-induced aggregation. Effects of oral PGE2 on secondary aggregation appears to be more clinically important because of its role in thrombus formation. The study shows that oral PGE2 for labor induction possesses anti-thrombotic properties and may be useful in reducing the incidence of thromboembolic complication of labor and puerperium.
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PMID:The effects on platelet aggregation of oral prostaglandin E2 used for the induction of labour. 113 35

Administration (ip) into fed mice of glucagon, epinephrine, vasopressin, oxytocin, angiotensin II, and dibutyryl cyclic AMP (dbcAMP) resulted in a rapid (within 2.5 to 15 min) elevation of PRPP content (two- to threefold) and in acceleration of the rate of de novo purine synthesis (twofold). Inhibition of the epinephrine-stimulated glycogenolysis by 2,5-anhydromannitol diminished markedly the acceleration effect of the hormone on the rate of purine synthesis. Administration of the hormones caused a rapid rise in the liver content of glucose 6-phosphate (G6P) by 15-70% but did not increase the ribose 5-phosphate (R5P) content. Liver ATP content was not affected. The hormones did not cause direct activation of PRPP synthetase, as gauged by the specific activity of the enzyme, its Km for substrates R5P and ATP, and its sensitivity to inhibition by ADP and GDP. The hormones did not increase the liver content of the enzyme activators Pi and Mg2+. The results suggest that the glycogenolytic hormones accelerate purine synthesis by a metabolic mechanism associated with the enhancement of glycogenolysis. PRPP synthesis is probably enhanced by the glycogenolysis-induced alterations in the cellular content of some metabolites other than R5P.
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PMID:Acceleration of purine synthesis in mouse liver by glycogenolytic hormones. 172 6

Some studies have indicated that insulin was able to increase the level of free cytosolic calcium in adipocytes [e.g. 7]. The present study was designed to examine this phenomenon. Insulin did not increase free cytosolic calcium, however oxytocin, vasopressin, alpha-adrenergic agonists and ATP did increase free cytosolic calcium in adipocytes. Other agonists which also did not alter calcium were epidermal growth factor, angiotensin II, glucagon, and beta-adrenergic agonists. The effect of oxytocin at increasing free cytosolic calcium was inhibited by activation of protein kinase C with phorbol 12-myristate 13-acetate and by ADP ribosylation of a Gi like protein with islet activating protein. The hormones that did increase cytosolic free calcium did so by mobilizing internal calcium and by promoting calcium influx. Even though insulin did not increase free cytosolic calcium, it was able to attenuate the alpha-adrenergic mediated increase in cytosolic free calcium. The fact that certain hormones can increase the level of the second messenger calcium in adipocytes implies that it may be a key intracellular regulator of adipocyte function as it is in many other tissues.
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PMID:Effect of hormones on cytosolic free calcium in adipocytes. 251 19

Human amnion is hypothesized to be a target tissue for hormone messages from the fetus regarding labor. We have previously demonstrated prostaglandin E2 (PGE2) release in amnion after treatment with phorbol and oxytocin, but other potential agonists of the inositol phospholipid/protein kinase-C system have not been investigated. The effects of extracellular ATP on cytosolic calcium concentration [( Ca2+])i) inositol phosphate (IP) accumulation, and PGE2 production were studied in cultured human amnion cells. Intracellular free calcium [Ca2+]i was measured using the fluorescent dye fura-2. Addition of 0.01-30 microM ATP resulted in a [Ca2+]i transient which peaked within 15 sec and returned to baseline over 10 min. UTP (1 microM) was more effective than ATP (1 microM); [Ca2+]i levels rose from 233 to 2880 nM (UTP) and 2320 nM (ATP). A reduced effect was observed with other nucleotides in a rank order of agonist potency of ITP greater than CTP greater than ADP greater than GTP greater than TTP. No effect was seen with AMP, cAMP, or adenosine. This is consistent with P2 purinoceptors, as described in other tissues. ATP (100 microM) also dramatically increased IP accumulation. Inositol triphosphate, inositol bisphosphate, and inositol monophosphate were increased 7-, 9-, and 16-fold respectively. The agonist potency order of other nucleotides for IP accumulation was the same as that of [Ca2+]i. Pharmacological concentrations of ATP (1 mM) were required to increase PGE2 production. Many other nucleotides were equally effective at this concentration. ATP activates the phospholipase-C system in human amnion, as demonstrated by the increase in [Ca2+]i and inositol phosphates. The physiological significance of purinergic stimulation of this tissue remains unclear.
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PMID:Adenosine triphosphate activates the phospholipase-C cascade system in human amnion cells without increasing prostaglandin production. 292 32

Membrane fractions prepared from the uterine endometrium of untreated ovariectomized sheep contained a 41 x 10(3) Mr protein that was [32P]ADP-ribosylated by pertussis toxin in the presence of [32P]NAD. Progestin and progestin plus oestrogen treatment in vivo increased the concentration of this protein 2.7- and 3.6-fold respectively. Endometrial extracts from untreated or progestin-treated sheep also contained proteins of Mr 69 x 10(3) and 120 x 10(3) which were ADP-ribosylated in the absence of pertussis toxin; these proteins were not ADP-ribosylated in sheep receiving oestrogen. Incubation of endometrial slices from progestin plus oestrogen-treated sheep with oxytocin in vitro increased phosphoinositide hydrolysis 11-fold. This effect was not altered by prior incubation with pertussis toxin, although toxin treatment reduced by 64% subsequent labelling of the 41 x 10(3) Mr protein when membrane fractions prepared from pretreated slices were incubated with pertussis toxin and [32P]NAD. Thus the endometrium contains a pertussis toxin-sensitive protein which is induced by steroid treatment, but this protein is not involved in the phosphoinositide response to oxytocin.
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PMID:Pertussis toxin-catalysed ADP-ribosylation of endometrial proteins in sheep. 339 97

The release of prostacyclin from chopped myometrial fractions of 18-20 day pregnant rats was assayed by inhibition of ADP-induced aggregation of citrated rabbit platelet-rich plasma. Preincubation of myometrial tissue with oxytocin 10 mU/ml increased prostacyclin generation from 2.25 +/- 0.48 (control) to 3.75 +/- 0.73 ng/mg over 15 minutes. Bradykinin 20 microgram/ml also caused a significant increase in myometrial prostacyclin output from 2.26 +/- 0.19 to 4.26 +/- 0.64 ng/mg. PGF2 alpha 1 microgram/ml did not increase prostacyclin release significantly. Pretreatment of myometrial tissue with the phospholipase inhibitor mepacrine significantly reduced the peptide-stimulated release of prostacyclin. The results suggest that prostacyclin production may play an important role in modulating the actions of oxytocin and bradykinin in the pregnant rat myometrium.
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PMID:Effects of uterine stimulant drugs on prostacyclin production by the pregnant rat myometrium. I. Oxytocin, bradykinin and PGF2 alpha. 699 22

Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial membranes with iodinated oxytocin antagonist (OTA), followed by detergent solubilization and size selection, showed that radioactivity eluted in two distinct peaks: one corresponding in size to the isolated receptor (approximately 60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT) increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold in a dose-dependent manner. The effects of OT were blocked by coincubation with OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak were identified by immunoadsorption. Significant amounts of both G alpha q/11 and G alpha i3 were associated with the OTR; a lesser amount of G alpha s was complexed. Using the same approach but with antibodies to effector enzymes, we observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated with the OTR. The results corroborate the well-established interaction of OTR with Gq and further show that Gi coupling might be an important component of OTR signal transduction. To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT treatment. These findings with pertussis toxin strongly indicate that OTR is coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled receptor) was demonstrable in the myometrium only before the end of gestation and after parturition and accounted for about one-half the 125I-OTA binding activity. At term, there was about a fivefold increase in binding and almost a complete shift to the 240- to 320-kDa-size complex. Thus the established increased sensitivity of the myometrium to OT at term could be the result of both upregulation of OTRs and an increase in the fraction of receptors coupled to signal transduction components, one of which is Gi.
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PMID:Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. 917 88

Mammary myoepithelial cells were isolated and cultured to characterize their properties. The intracellular calcium concentration (Cai2+) was measured using the ratio of fura-2 fluorescence at 340 nm to that at 360 nm (F340/F360), and the contraction was simultaneously monitored by the change of fluorescence intensity at 360 nm (F360). Cultured myoepithelial cells retained their contractile machinery as in the intact tissue. NBD-phallacidin fluorescence, which marks F-actin, and electron microscopy showed abundant bundles of microfilaments in the cytoplasm. Oxytocin (> 0.1 nM) induced an increase in Cai2+ and contraction. The amplitude and time course of the Cai2+ increase were not markedly affected in the Ca2+-free solution. Nifedipine (10 microM) did not affect the response to oxytocin. ATP (>1 microM) induced an increase in Cai2+ and contraction. The response to ATP was not affected by Ca2+ removal, but was suppressed by suramin (100 microM), an antagonist of P2-purinergic receptors. The order of potency of nucleotides to increase Cai2+ was ATP = ADP > UTP > UDP. These findings indicate the presence of P2-purinergic receptors in mammary myoepithelial cells. The results suggest that stimulant-induced Cai2+ increases and contractions are due to release of Ca2+ from intracellular stores in these cells. In addition to the hormonal action of oxytocin, extracellular nucleotides may function as paracrine agents to contract myoepithelial cells in the mammary gland.
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PMID:Involvement of P2-purinergic receptors in intracellular Ca2+ responses and the contraction of mammary myoepithelial cells. 935 97

Oxytocin (OT) induces PG synthesis by both uterine endometrial and amnion cells. We showed previously that CHO cells stably transfected with the rat oxytocin receptor (CHO-OTR cells) also synthesize PGE2 in response to OT. In the present work we have demonstrated that OTRs are coupled to both Gi and Gq/11, using immunoprecipitation of solubilized OTR complexes and ADP ribosylation. OT treatment caused the rapid phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2 or p42MAPK), which was partially inhibited by pertussis toxin (PTX), consistent with OTR-Gi coupling. The PTX-insensitive portion of ERK2 phosphorylation was linked to Gq, as inhibitors of both phospholipase C (U-73122) and protein kinase C (GF-109203X) blocked OT-induced ERK2 phosphorylation. OT-stimulated c-fos expression was also mediated by ERK2 phosphorylation. The ERK-c-fos pathway has been shown to be associated with cell proliferation, but OT had no effect on [3H]thymidine uptake by CHO-OTR cells. However, inhibition of OT-induced ERK2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly reduced OT-stimulated PGE2 synthesis, pointing to the importance of ERK2 activation in OT action.
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PMID:ERK2 mediates oxytocin-stimulated PGE2 synthesis. 957 24


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