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)

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

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

1 Eicosatetraynoic acid, the acetylene analogue of arachidonic acid, which inhibits both the cyclo-oxygenase and lipoxygenase pathways, reduced the contractile response of rat uterine smooth muscle to either angiotensin II or oxytocin. 2 Indomethacin, an inhibitor of cyclo-oxygenase, did not reduce the response to angiotensin II but did abolish the contractile response to low doses of oxytocin. 3 Nordihydroguaiaretic acid, a lipoxygenase inhibitor, totally abolished the uterine response to either oxytocin or angiotensin II. 4 The contractile response to carbachol, a cholinoceptor agonist, was unaffected by pretreatment with any of the cyclo-oxygenase or lipoxygenase inhibitors. 5 From these findings, it can be implied that some product of the arachidonate lipoxygenase pathway augments peptide-induced contractions of the rat uterus.
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PMID:Prostaglandin synthesis inhibitors: effect on angiotensin II- and oxytocin-induced contractions in rat uterine smooth muscle. 687 37

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