Effect of trifluoperazine, a calmodulin antagonist, on prostaglandin output from the guinea-pig uterus.
Trifluoperazine, a calmodulin antagonist, inhibited the A23187-induced increase in outputs of prostaglandin (PG) F-2 alpha and 6-oxo-PGF-1 alpha from the Day 7 and Day 15 guinea-pig uterus superfused in vitro. The basal outputs of, and the arachidonic acid-induced increase in outputs of PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha from the guinea-pig uterus were not inhibited by trifluoperazine. In contrast, indomethacin inhibited A23187-stimulated, arachidonic acid-stimulated and the basal outputs of PGs from the guinea-pig uterus, indicating that trifluoperazine was not inhibiting cyclo-oxygenase. Since the action of A23187 is dependent upon extracellular Ca2+, the present findings provide evidence that calmodulin is involved in Ca2+-induced increases in uterine PG output from the guinea-pig uterus. Trifluoperazine, but not indomethacin, inhibited A23187-induced contraction of the guinea-pig uterus, which is consistent with calmodulin being involved in smooth muscle contraction. Arachidonic acid treatment did not contract the guinea-pig uterus. These findings indicate that PGs are not involved in the contraction induced by A23187. Other findings of interest were (i) trifluoperazine caused a small, sometimes significant (P less than 0.05), increase in uterine PG output, (ii) exogenous arachidonic acid failed to increase PGF-2 alpha output from the Day 15 uterus in contrast to the stimulant action of A23187, and (iii) exogenous arachidonic acid caused a fairly large increase in uterine PGE-2 output in contrast to the small effect with A23187.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003864:Depression, Chemical; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000378:metabolism*
D001095:Arachidonic Acids; D002147:Calmodulin; D011458:Prostaglandins E; D011460:Prostaglandins F; D014268:Trifluoperazine; D016718:Arachidonic Acid; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone