External calcium dependence of the uterine contraction induced by prostaglandins E2 and F2 alpha and its antagonism with natural progestins.
Prostaglandins (PGs) E2 and F2 alpha are strong inducers of uterine contraction by promoting a Ca2+ increase into the cell through specific receptors coupled with the calcium channels. On the contrary, progesterone and 5 beta-reduced progestins promote smooth muscle relaxation by blocking the ion calcium influx. Thus, this study was designed to emphasize the importance of external calcium in the PGs-induced rat uterus contraction. Likewise, also studied was the antagonism and the interaction between PGs and progestins (progesterone and its 5 alpha and 5 beta-reduced derivatives) in the myometrium. Results showed that uterine contraction induced by PGs depends on external calcium, since verapamil or extracellular calcium depletion abolished the PGs effect. Regarding the PGs-progestins antagonism, it was observed that pregnanedione, pregnanolone and epipregnanolone were quite effective for counteracting of PGs-induced contraction. However, progesterone was effective in a middle range, whereas 5 alpha-reduced progestins (allopregnanedione and allopregnanolone) were almost ineffective. It has been concluded that the participation of PGs and progestins in the modulation of uterine contraction might be achieved through the control of calcium influx by opening (PGs) or blocking (progestins) receptor-operated calcium channels.
Perusquia
M
M
Unidad de Investigacion Biomedica, IMSS, Mexico City, Mexico.
Kubli-Garfias
C
C
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects* / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D011372:Progestins; D015237:Dinoprost; D014700:Verapamil; D015232:Dinoprostone