Mepacrine inhibition of bradykinin-induced contractions of the rabbit ear vein.
Bradykinin induced concentration-dependent contractions in spiral strip preparations of the central vein of rabbit's ears. These contractions require the presence of Ca2+ in the extracellular medium. Mepacrine (2.1 to 42.3 mumol/l) significantly reduced these contractions. Since indomethacin (28 mumol/l) did not reduce the contractions produced by bradykinin, the effect of mepacrine is not explained by inhibition of prostaglandin synthesis. Procaine (10(-7) to 10(-4) mol/l) did not reduce the contractions produced by bradykinin and thus is does not seem that mepacrine acts through a non-specific, local anaesthetic effect. Mepacrine reduced the phosphatidate-mediated transfer of 45Ca from an aqueous phase to an organic phase. It has recently been proposed that phosphatidate may be the Ca2+ ionophore in smooth muscle. However, in the present experiments procaine was about as potent as mepacrine in inhibiting phosphatidate-mediated 45Ca transfer, and since it did not reduce the contractile responses these results do not support the concept that mepacrine inhibits contractions by reducing the Ca2+ influx via a phosphatidate ionophore.
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism; D004431:Ear, External / Q000098:blood supply; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010712:Phosphatidic Acids / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology*; D011817:Rabbits; D014680:Veins / Q000187:drug effects
D010712:Phosphatidic Acids; D011796:Quinacrine; D001920:Bradykinin; D002118:Calcium