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.