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)

Early corpus luteum development in nonpregnant and pregnant goats was characterized by a steady increase in peripheral plasma concentrations of progesterone and a high release of prostacyclin (PGI-2) but low release of prostaglandin F-2 alpha (PGF-2 alpha). Jugular administration of oxytocin antagonist (OXA) (0.2 microgram/kg/day) on the day of oestrus and for 3 days thereafter to cyclic and mated goats, significantly (P less than 0.001) inhibited progesterone and prostaglandin secretion and reduced conception rate. Co-administration of PGI-2 (200 micrograms/day) with OXA resulted in a steady increase of progesterone and establishment of pregnancy, but co-administration of PGF-2 alpha (175 micrograms/day) with OXA had no effect. It is suggested that oxytocin is required for early development of the corpus luteum and such effects may be mediated via PGI-2 production.
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PMID:Inhibition of luteal function by oxytocin antagonist in goats (Capra hircus). 155 89

Blood samples were collected frequently from permanent catheters placed in the aorta and caudal vena cava of 36 heifers in order to monitor the release pattern of LH, FSH, progesterone, oestradiol-17 beta, oxytocin, PGF-2 alpha, PGE-2 and PGI-2 (determined as its 6-keto-PGF-1 alpha metabolite). The frequency of secretory bursts of both gonadotrophins and progesterone was similar in early pregnant and cyclic animals, whereas the amplitude of LH and progesterone increased between 2 and 4 weeks of gestation. Concentrations of circulating oestradiol-17 beta and oxytocin were already lower at Days 4-7 in pregnant than in cyclic animals. Oestradiol-17 beta originated after Day 14 from the uterus rather than the ovary. A sustained release of oxytocin most probably from the posterior pituitary gland and a concomitant decrease of progesterone occurred in about two-thirds of pregnant animals during Days 19-23. Insemination could induce releases of PGF-2 alpha lasting up to 2 h. In addition, basal concentrations of PGF-2 alpha during the first 6 days after oestrus were approximately 2-fold higher in inseminated than in non-inseminated cyclic heifers. A parallel increase of PGF-2 alpha and PGI-2 occurred between Days 30 and 33 of gestation. Early embryonic mortality resulted, at least up to Day 35, in 4-7 concomitant secretory bursts of PGF-2 alpha and luteal oxytocin. There was a delay of 20-26 h between the first and second release. The present results from in-vivo experiments point towards major endocrine changes in cattle within a few days after conception, resulting in an early inhibition of follicular oestradiol-17 beta and luteal oxytocin facilitating the suppression of luteolytic releases of PGF-2 alpha.
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PMID:Sequences of pituitary, ovarian and uterine hormone secretion during the first 5 weeks of pregnancy in dairy cattle. 250 92

Jugular administration of 200 micrograms PGI-2 salt significantly reduced spontaneous uterine activity in ovariectomized, oestrogen-primed goats; the effect was acute and persisted for about 3 h. Peripheral plasma concentrations of 6-keto-PGF-1 alpha, the stable metabolite of PGI-2, decreased to 50% of initial values after 30 min; but at the start of uterine recovery were in excess of 2 ng.ml-1. Uterine reactivity to both oxytocin and PGF-2 alpha after PGI-2 administration was unaffected.
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PMID:Effect of PGI-2 on uterine activity in vivo in non-pregnant ovariectomized goats (Capra hircus). 251 31

Five new concepts concerning the control of corpus luteum function in the cow have been developed in recent years. Prostacyclin (PGI-2) plays a luteotrophic role. Conversely, products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5 hydroxyeicosatetraenoic acid (5-HETE), play luteolytic roles. Luteal cells arise from two sources. The small luteal cells are all of theca cell origin; the large cells found early in the cycle (Days 2-6) are mainly of granulosa cell origin. However, a population of large cells found after Day 10 of the cycle are of theca cell origin. Oxytocin of luteal cell origin plays a role in development of the corpus luteum and possibly in its regression. The recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system, as well as the LH-cAMP system, is involved in control of progesterone synthesis in the bovine corpus luteum. Progesterone synthesis in the small theca-derived luteal cells is primarily controlled by the cAMP system. However, elevated intracellular calcium diminishes cAMP-mediated progesterone synthesis in these cells. These findings modify our current concepts of the mechanisms of control of progesterone secretion by the corpus luteum and suggest several new lines of research.
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PMID:Hammond memorial lecture. New concepts of the control of corpus luteum function. 302 24

The effects of PGI-salt and PGI-2 methyl ester on intrauterine pressure (IUP) and uterine electromyographic activity (EMG) were examined in vivo in non-pregnant ovariectomized sheep. PGI-2 salt and PGI-2 methyl ester (50--200 micrograms) reduced significantly the frequency and amplitude of IUP cycles and also inhibited the associated uterine EMG activity. Injections of oxytocin (50 mU) or PGF-2 alpha (2 micrograms) partly overcame the inhibiton of IUP induced by the PGI-2 methyl ester. These results suggest that endogenous PGI-2 may be involved in the regulation of uterine activity in sheep.
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PMID:Inhibition by PGI-2 of myometrial activity in vivo in non-pregnant ovariectomized sheep. 675 Jan 8

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8 +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue, iloprost, can induce U-AQP2 excretion independent of AVP.
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PMID:Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in humans. 1205 53

Efficient RIA procedures are required for determination of prostaglandins (PGF(2alpha), PGE(2), PGI(2) and their metabolites) in bovine blood plasma to elucidate their significance in reproductive endocrinology. A new rapid efficient prepurification was developed using commercial octadecyl silicagel cartridges. Prepurification is especially necessary for the determination of 13,14-dihydro-15-keto-PGE(2) (PGEM). After prepurification, PGEM was first converted into the more stable 13,14-dihydro-15-keto-PGA(2) (PGAM) and measured in a RIA-system for PGAM. For PGF(2alpha), 13,14-dihydro-15-keto-PGF(2alpha) (PGFM), PGE(2) and 6-keto-PGF(1alpha) direct tests using 50 mul plasma per tube were elaborated. The validity of the tests was monitored by high performance liquid chromatography radioimmunoassay (HPLC RIA ). Infusion studies using PGF(2alpha) and PGE(2) showed that about 10% of these hormones remained unmetabolized after the first passage through the lungs. The biological half life of the metabolites PGFM and PGEM in bovines was estimated to be 4 min. Thus, PGFM and PGEM measurements in the peripheral circulation reflect even short-term secretory changes of PGF(2alpha) and PGE(2). During the infusion of PGF(2alpha) the levels of progesterone decreased but were not affected by PGE(2). Both prostaglandins caused increased oxytocin secretion. In the cow peripartum first PGEM elevations were measured 5 to 8 d ante partum, whereas PGFM increased 1 to 2 d ante partum. Then both prostaglandins increased simultaneously until parturition. In the postpartal phase PGFM was higher than PGEM, and both prostaglandins remained elevated for several days. Prostacyclin levels remained unchanged during the peripartal period.
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PMID:Improvement of radioimmunoassays for prostaglandins in bovine blood plasma and their application to monitor reproductive functions. 1672 87

Vasopressin type 2 receptor (V2R) exhibits mostly important properties for hydroosmotic equilibrium and, to a lesser extent, on vasomotricity. Drugs currently acting on this receptor are analogs of the natural neuropeptide, arginine vasopressin (AVP), and hence are competitive ligands. Peptides that reproduce specific sequences of a given receptor have lately been reported to interfere with its action, and if such molecules arise from regions remote from the binding site they would be anticipated to exhibit noncompetitive antagonism, but this has yet to be shown for V2R. Six peptides reproducing juxtamembranous regions of V2R were designed and screened; the most effective peptide, cravky (labeled VRQ397), was characterized. VRQ397 was potent (IC(50) = 0.69 +/- 0.25 nM) and fully effective in inhibiting V2R-dependent physiological function, specifically desmopressin-L-desamino-8-arginine-vasopressin (DDAVP)-induced cremasteric vasorelaxation; this physiological functional assay was utilized to avoid overlooking interference of specific signaling events. A dose-response profile revealed a noncompetitive property of VRQ397; correspondingly, VRQ397 bound specifically to V2R-expressing cells could not displace its natural ligand, AVP, but modulated AVP binding kinetics (dissociation rate). Specificity of VRQ397 was further confirmed by its inability to bind to homologous V1 and oxytocin receptors and its inefficacy to alter responses to stimulation of these receptors. VRQ397 exhibited pharmacological permissiveness on V2R-induced signals, as it inhibited DDAVP-induced PGI(2) generation but not that of cAMP or recruitment of beta-arrestin2. Consistent with in vitro and ex vivo effects as a V2R antagonist, VRQ397 displayed anticipated in vivo aquaretic efficacy. We hereby describe the discovery of a first potent noncompetitive antagonist of V2R, which exhibits functional selectivity, in line with properties of a negative allosteric modulator.
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PMID:VRQ397 (CRAVKY): a novel noncompetitive V2 receptor antagonist. 1964 Nov 30

Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI(2) , acting via cAMP/PKA, was found to increase contraction-associated protein expression in myometrial cells and to promote oxytocin-driven myometrial contractility. Cyclo-oxygenase-2 (COX-2) is the rate-limiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX-2 expression, synthesis and activity. Three cAMP agonists (8-bromo-cAMP, forskolin and rolipram) increased COX-2 mRNA expression and further studies confirmed that this was associated with COX-2 protein synthesis and activity (increased PGE(2) and PGI(2) in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMP-effectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMP-effector PDZ-GEF(1-2) , without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX-2 expression and that PGE(2) acts through EP-2 to activate MAPK and increase COX-2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.
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PMID:Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells. 2185 42