Different mechanism of relaxation induced by aporphine alkaloids in rat uterus.
We have examined the uterine relaxant action of three aporphine molecules (S-glaucine, S-boldine and R-apomorphine) in two experimental conditions, with and without calcium in the bathing solution, and compared these effects with those obtained with the calcium antagonists verapamil and diltiazem. The present study shows that the alkaloids relax the uterine muscle but with different mechanisms of action. In Ca(2+)-containing solution all three alkaloids relaxed the uterus previously contracted by KCl or acetylcholine, but in Ca(2+)-free medium only R-apomorphine was able to relax oxytocin-induced contraction. The calcium antagonists, verapamil and diltiazem, relaxed KCl- or acetylcholine-induced contraction in Ca(2+)-containing solution, whereas they only relaxed oxytocin-induced contraction in Ca(2+)-free medium at much higher doses. These results suggest that glaucine and boldine behave as specific calcium entry blockers without affecting the contractile machinery or intracellular Ca2+ levels as apomorphine does. The absolute configuration (S-glaucine and S-boldine vs R-apomorphine) may account for this different action.
Ivorra
M D
MD
Department de Farmacologia, Facultat de Farmacia, Universitat de Valencia, Spain.
Martinez
F
F
Serrano
A
A
D'Ocon
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001060:Aporphines / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003470:Culture Media; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*
D001060:Aporphines; D002121:Calcium Channel Blockers; D003470:Culture Media; D010121:Oxytocin; D011189:Potassium Chloride; C011686:boldine; D001058:Apomorphine; D000109:Acetylcholine; C005004:glaucine; D002118:Calcium