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)

The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10(-3) M EGTA. Okadaic acid (5 x 10(-6) to 5 x 10(-5) M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 x 10(-5) M, to 142.3 +/- 6.1% (n = 7) of the contraction induced by oxytocin 10(-6) M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca(2+)-free medium containing 10(-3) M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M) significantly reduced, in a Ca(2+)-containing medium, the maximum contractile effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium, theophylline 3 x 10(-3) M and caffeine 10(-2) M did not modify the maximum effect of OA 10(-5) M but shortened the time to peak tension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium. 782 49

In the present study, we examined the effects of okadaic acid, a selective inhibitor of type 1 and 2A protein phosphatases, on the mechanical responses evoked by oxytocin, K(+)- and Na(+)-modified solutions and ouabain in estrogen-primed rat myometrium. Oxytocin elicited a rapid, phasic contraction followed by rhythmic oscillations. The phasic response was partially resistant to the absence of external Ca2+. Okadaic acid (1 microM) and the L-type calcium channel blocker nifedipine (1 microM) abolished the oscillatory component and reduced the initial, phasic response to about 80% of the control response. High K+ (60 mM) solution, ouabain (1 mM), K(+)-free medium and low Na+ (25 mM) solution induced extracellular Ca(2+)-dependent biphasic responses composed by an early rapid (KCl, ouabain and K(+)-free solution) or slower developed (25 mM Na+ solution) phasic contraction followed by a sustained increase in tension. Okadaic acid and nifedipine, alone or in combination, abolished or decreased similarly the contractile response evoked by these stimulants. The okadaic acid- and nifedipine-insensitive responses to ouabain, K(+)-free and low Na+ solution were enhanced by increasing the extracellular concentration of Ca2+ in the medium and were inhibited in a dose-dependent manner by amiloride (0.05-0.5 mM). These data suggest that, in estrogen-primed rat uterus, dephosphorylating mechanisms by OA-sensitive protein phosphatases play an important role in regulating myometrial contractions elicited by Ca2+ entry through voltage-sensitive Ca2+ channels.
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PMID:Inhibitory effects of okadaic acid on rat uterine contractile responses to different spasmogens. 918 76

Reversible phosphorylation is essential in regulating uterine contractions. Identification, characterization, and functional understanding of myometrium protein phosphatase(s) are lacking. Okadaic acid (OA), which inhibits protein phosphatase-1 (PP1) and PP2A, has been shown to alter uterine contractions. Experiments were conducted to determine the 1) identity of the myometrial OA-sensitive PP, 2) influence of OA on spontaneous and oxytocin (OT)-stimulated myometrial contractions, and 3) expression of uterine PPs during sexual development. Western blot analysis indicated the presence of PP1(alpha) and PP2A in immature and mature mice. As determined by immunohistochemistry, gonadotropin-stimulated adult mouse uteri contain PP1(alpha) in longitudinal and circular myometrial layers and endometrial epithelium. Conversely, PP2A was localized to the endometrial stroma. Cumulative addition of OA (n = 9; 10, 100, 250, 500, 1000 nM) did not significantly alter spontaneous contractions of mouse uterine horns in comparison to vehicle-treated controls (n = 9). By the end of the test period OA- and vehicle-treated uteri displayed a comparable decline in uterine contractions to 79.2% and 63.7%, respectively, of basal contractile activity. Pretreatment of uterine tissue with OA (1 microM; n = 7) significantly reduced contractile response to increasing concentrations of OT (8, 16, 32, 64 nM) in comparison to vehicle pretreatment (dimethyl sulfoxide; n = 7). At the end of the OT-administration period, contractile activity was 160.4% and 67.3% of basal contractile activity for vehicle (no OA) and OA-pretreated groups, respectively. During the early prepubertal period PP1(alpha) was expressed in longitudinal myometrium and absent in circular myometrium; whereas, during the transition to sexual maturity PP1(alpha) was observed in both the longitudinal and circular myometrium. In summary, these studies have indicated 1) that PP1 is the primary myometrial OA-sensitive PP; 2) that inhibition of PP1 had no effect on spontaneous contractions, whereas it markedly inhibited OT-stimulated uterine contractions; and 3) that PP1 is differentially expressed in the circular and longitudinal myometrium in relation to sexual development.
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PMID:Divergence in murine myometrium spontaneous and oxytocin-stimulated contractile responses to serine/threonine protein phosphatase-1 inhibition. 1095 21