Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nafazatrom inhibits, in a dose-dependent way, the amplitude and frequency of the rhythmic contractions induced by oxytocin (4 mU/ml), as well as the methacholine (10(-5) M)- and CaCl2 (10 mM)-induced contractions, and the phasic response to KCl (60 mM); similarly, it inhibits the tonic contraction induced by KCl (60 mM) and oxytocin (10 mU/ml). A single concentration of nafazatrom (10(-4) M) also inhibits the uterine contractions caused by carbachol (10(-4) M) and prostaglandin F2 alpha (10(-6) M). CaCl2 (0.1-10 mM) only partially reverses the inhibition produced by nafazatrom on the KCl-induced tonic contractions. Bay K 8644 (3 x 10(-10)-3 x 10(-7) M) reverses the inhibition by 10(-4) M but not by 3 x 10(-4) M of nafazatrom on the CaCl2-induced contractions. Nafazatrom also inhibits, in a dose-dependent way, the calmodulin-dependent phosphodiesterase activity. Our results would suggest that, independently of its 5-lipoxygenase blocking activity, nafazatrom inhibits the contractions of the rat uterus by inhibiting the calmodulin activity and, presumably, by reducing the influx of extracellular calcium and/or the mobilization of intracellular calcium.
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PMID:Mechanism of nafazatrom-induced inhibition of rat uterus contractions in vitro. 256 Mar 65

The involvement of arachidonic acid and arachidonic acid metabolites in the control of oxytocin secretion by ovine corpus luteum was investigated, using slices of luteal tissue incubated in vitro. Oxytocin was secreted at steady rates by luteal slices, during 60-min incubations (315.0 +/- 45.3 pg/mg.h). The secretion of oxytocin was stimulated by arachidonic acid, phospholipase A2 (PLA2), and phospholipase C (PLC) in a dose-dependent manner. The highest doses of arachidonic acid, PLA2, and PLC used stimulated oxytocin secretion by 145.8 +/- 23.0% (P less than 0.01; n = 6), 331.5 +/- 42.4% (P less than 0.02; n = 4), and 955.5 +/- 278.6% (P less than 0.01; n = 4), respectively. Oxytocin secretion by luteal slices was not affected by either prostaglandin F2 alpha (PGF2 alpha) or PGE2 over a concentration range from 3-3000 nM. Furthermore, inhibitors of the cyclo-oxygenase pathway of arachidonic acid metabolism did not consistently affect arachidonic acid and PLA2-stimulated oxytocin secretion. Nordihydroguaiaretic acid, which inhibits 5-lipoxygenase, however, totally abolished arachidonic acid- and reduced PLA2-stimulated oxytocin secretion. The presence of CoCl2 in the incubation medium also significantly reduced basal and PLA2- and PLC-stimulated oxytocin secretion [P less than 0.05 (n = 5), P less than 0.05 (n = 5), and P less than 0.01 (n = 6), respectively]. We have shown that oxytocin secretion from slices of ovine corpus luteum incubated in vitro is stimulated by exogenous and endogenously released arachidonic acid. The data show that PGF2 alpha and PGE2 do not have a role in luteal oxytocin secretion in vitro and PG formation does not appear to be involved in the stimulation of oxytocin secretion elicited by arachidonic acid or PLA2. Arachidonic acid may have its effect via the lipoxygenase pathway.
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PMID:Control of oxytocin secretion by ovine corpora lutea: effects of arachidonic acid, phospholipases, and prostaglandins. 312 41

Intrauterine administration of nordihydroguaiaretic acid (NDGA) will maintain luteal function in sheep and also suppress the release of both oxytocin and prostaglandin F2 alpha (PGF2 alpha) suggesting that 5-lipoxygenase products of arachidonic acid may be involved in ovine luteolysis. During luteolysis, uterine PGF2 alpha is considered to be the major stimulus for the secretion of luteal oxytocin, and we report the effects of 5-lipoxygenase inhibition, via intrauterine NDGA administration, on the ability of PGF2 alpha to effect such secretion. In the NDGA-treated ewes, luteal function was maintained and oestrus delayed, the duration of the oestrous cycle (20 +/- 1 days; mean +/- S.D.; n = 9) being significantly (P < 0.01) longer than in intact controls (15 +/- 1 days, n = 4). Jugular infusions of PGF2 alpha did not stimulate luteal secretion of oxytocin, the effects being comparable with those in ovariectomized ewes. In intact ewes receiving intrauterine infusions of vehicle only, PGF2 alpha produced marked increases in luteal secretion of oxytocin. Also, preinfusion or basal concentrations of oxytocin in this group of ewes (6.6 +/- 1.9 pg/ml) were significantly (P < 0.01) greater than in either the NDGA-treated (3.1 +/- 1.1 pg/ml) or ovariectomized (3.0 +/- 0.6 pg/ml) ewes. The results suggest involvement of 5-lipoxygenase products of arachidonic acid in the release of oxytocin from the ovine corpus luteum.
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PMID:Potential role for lipoxygenase products of arachidonic acid in prostaglandin F2 alpha-stimulated oxytocin release from the ovine corpus luteum. 796 83

The effect of an intra-luteal injection of the 5-lipoxygenase (5-LO) inhibitor BWA4C (2 mg in 50 microl DMSO) on the secretion of oxytocin (OT) from the corpus luteum in response to a close-arterial infusion of prostaglandin (PG)-F2alpha (5 ng min(-1)) was examined in anaesthetised sheep. Within 30 minutes of administration both basal (pre-infusion) and PGF2alpha-stimulated OT release into the posterior vena cava were significantly (P<0.01) reduced. These results are consistent with the proposition that 5-LO products of arachidonic acid may modulate OT secretion from the ovine corpus luteum.
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PMID:Suppression of ovarian oxytocin secretion after intra-luteal administration of the arachidonate 5-lipoxygenase inhibitor BWA4C in the ewe. 969 Jun 15

Intrauterine administration of nordihydroguaiaretic acid (5 mg, bid. NDGA), an inhibitor of the enzyme 5-lipoxygenase, on days 10-14 of the oestrous cycle, maintained luteal function and delayed oestrus in the ewe. The duration (mean +/- SD) of the oestrous cycle in the treatment group (n = 4) was 24 +/- 1 days, which was significantly (P < 0.001) longer than that of 16 +/- 1 days in vehicle-treated controls (n = 4); plasma progesterone concentrations were also significantly (P < 0.01) higher in the treatment group. On days 13 and 14 of the cycle (oestrus = Day 0) in the control group large pulses of 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) were evident, with mean (+/- SD) maximum concentrations of 232.5 +/- 66 and 415 +/- 309 pg ml(-1), respectively. In the treatment group, however, concentrations of PGFM were below detection level (< 50 pg ml(-1)). Similarly, in the control group, oxytocin release was highly pulsatile, with mean (+/- SD) peak concentrations of 21.8 +/- 5 and 18.5 +/- 6 pg ml(-1) on days 13 and 14, respectively; these were significantly (P < 0.01) higher than values of 7.6 +/- 3 and 6.1 +/- 3 pg ml(-1) in NDGA-treated ewes, where pulses were of relatively low amplitude. These results suggest that 5-lipoxygenase products of arachidonic acid metabolism may be involved in the positive feedback mechanism between luteal oxytocin and uterine PGF2alpha during luteolysis in the ewe.
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PMID:Delayed luteolysis after intra-uterine infusions of nordihydroguaiaretic acid in the ewe. 977 84

Intrauterine administration of the 5-lipoxygenase inhibitor nordihydroguariaretic acid (NDGA; 5 mg, bid) on Days 9-14 of the ovine estrous cycle (estrus = Day 0) delayed luteolysis and extended the duration of the estrous cycle (20+/-1, SD, vs. 16+/-1 days; P < 0.01). In control ewes, plasma concentrations of 13,14,dihydro-15-keto prostaglandin F2alpha increased significantly (P < 0.001) following i.v. administration of oxytocin (10 i.u.) on Day 14; in the nordihydroguariaretic acid-treated ewes, however, there was no such increase. In addition, concentrations of endometrial oxytocin receptors were significantly less (P < 0.01) in the nordihydroguariaretic acid-treated ewes (218+/-60 vs. 579+/-66 fmol/mg tissue). These results suggest that 5-lipoxygenase products of arachidonate metabolism may be involved in the control of ovine luteal function.
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PMID:Suppression of oxytocin-induced prostaglandin F2alpha release after intra-uterine nordihydroguariaretic acid administration in ewes. 1068 Jul 73