Pharmacological studies on supersensitization. X. Effect of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine on the utilization of calcium in acetylcholine-induced contraction of isolated vas deferens of guinea pig.

Abstract

Effects of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED) and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of guinea pig were examined. Tripelennamine and DBED potentiated the contractile responses to acetylcholine and potassium chloride in Ca2+-free Tyrode solution. DBPD potentiated the contractile responses to lower concentrations of acetylcholine in Ca2+-free Tyrode solution, but did not affect contractions induced by potassium and higher concentrations of acetylcholine in Ca2+-free Tyrode solution. In depolarized vas deferens, tripelennamine and DBED augmented the maximum response to Ca2+, while DBPD did not affect the maximum response to Ca2+ and decrease the sensitivity to Ca2+. The contractile responses to acetylcholine in standard Tyrode solution were attenuated by lanthanum chloride and the residual contractions were not affected by tripelennamine, DBED and DBPD or decreased by DBPD. The contractile responses to potassium chloride were completely abolished by lanthanum chloride. The half-time of decrease in acetylcholine-contraction in Ca2+-free Tyrode solution was significantly different from that of potassium-contraction in Ca2+-free Tyrode solution. The contractile response of the glycerinated muscle piece of vas deferens to calcium chloride was potentiated by DBED, but was not affected by tripelennamine and DBPD. These results suggest that tripelennamine and DBED facilitate nonselectively the transmembrane influx of calcium from extracellular fluid and superficial calcium-binding sites. In addition, DBED increases the sensitivity of contractile element to cytoplasmic free calcium ion. DBPD potentiates the contractile response without affecting the transmembrane mobilization of Ca2+ induced by excitation of cell membrane.