Opposite and mutually antagonistic effects on uterine contractility of two epimeric forms of a synthetic prostaglandin analog.
Comparisons were made of the ability of intravenous infusions of prostalene and PGF2 alpha to stimulate increases in uterine contractility in vivo in the 14 day pregnant hamster. Whereas PGF2 alpha gave a linear dose response over the range 0.25 to 6.25 microgram/min., to achieve 5 fold increase in uterine activity, prostalene induced a multiphasic dose response curve. Inhibition was observed at 0.01 microgram per min. followed by a shallow stimulatory dose response to 0.25 microgram/min. plateauing at 1.8 fold stimulation to at least 1.25 microgram per min. When the epimeric mixture was separated and the two 15 position epimers studied separately the reason for this atypical dose response curve became clear. The 15 alpha OH epimer induced a linear stimulatory dose response from 0.05 to 6.25 microgram per min. infusion rates to a 5 fold increase in uterine contractility. The 15 beta OH epimer, however, induced a linear inhibitory dose response over the range 0.4 to 50 ng/min. It was, therefore, apparent that the atypical dose response curve observed from the mixture was the resultant of two opposite and mutually antagonistic activities. The data suggests also that the inhibitory epimer is capable of antagonizing both endogenous and exogenous prostaglandin, probably by a mechanism of competitive inhibition.
D000818:Animals; D002260:Carboprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D011247:Pregnancy; D011460:Prostaglandins F / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D013237:Stereoisomerism; D014590:Uterine Contraction / Q000187:drug effects*
D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; D002260:Carboprost; C009981:prostalene