Effects of TMB-8, an intracellular calcium antagonist, and W-7, a calmodulin antagonist, on prostaglandin output from the guinea-pig uterus.
TMB-8, an intracellular Ca2+ antagonist, inhibited the A23187-induced increase in outputs of prostaglandin (PG) F-2 alpha and 6-keto-PGF-1 alpha from the guinea-pig uterus superfused in vitro. The high basal output of PGF-2 alpha from the Day-15 guinea-pig uterus was not inhibited by TMB-8, indicating that a maintained high intracellular free Ca2+ concentration is not necessary for maintaining this high output of PGF-2 alpha. W-7, a calmodulin antagonist, had similar actions except that PGF-2 alpha output from the Day-15 uterus was reduced 20-30 min after the W-7 treatment had stopped. Overall, these findings suggest that, in the guinea-pig, oestradiol acting on a progesterone-primed uterus causes a prolonged stimulation of endometrial phospholipase A-2 in the absence of a maintained high Ca2+ concentration, thus providing a continuous release of arachidonic acid for increased endometrial PGF-2 alpha synthesis during the last third of the oestrous cycle.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013449:Sulfonamides; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D015121:6-Ketoprostaglandin F1 alpha; D005707:Gallic Acid; C017967:W 7; D015237:Dinoprost; D015232:Dinoprostone