CALCIUM MODULATORY PROPERTIES OF 2,6-DIBUTYLBENZYLAMINE (B25) IN RAT ISOLATED VAS-DEFERENS, CARDIAC AND SMOOTH-MUSCLE PREPARATIONS

1 In rat isolated vas deferens the new compound 2,6-dibutylbenzylamine (B25) evoked a series of repeating rhythmic contractions. Concentration-response curves constructed for this effect were bell-shaped, indicating a biphasic effect for this compound. By contrast, B25 depressed heart contractility without any visible positive inotropic or chronotropic activity. 2 Experiments with tetrodotoxin, reserpine, capsaicin, alpha-adrenoceptor blocking compounds and other agents permit us to exclude a release of neuromediators or a direct stimulation of post-synaptic receptors to account for the rhythmic effect of B25 in the rat vas deferens. 3 In the same tissue, the increase in Ca-45(2+) uptake, the voltage-dependency as well as the dependence of the B25-induced rhythmic activity upon the external calcium concentration indicate a direct activation of voltage-sensitive calcium channels (VSCC). 4 Verapamil paradoxically stimulated the rhythmic effect of B25 in the rat vas deferens. La3+ was inactive while nifedipine was a weak inhibitor. By contrast Ni2+ and Mn2+ ions were good inhibitors (IC50 < 10(-4)M), suggesting that a possible opening of T-type VSCC underlies the rhythmic effect of B25. 5 In radioligand binding studies competition experiments with [H-3]-nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine-sensitive binding sites of heart and vas deferens smooth muscle. 6 B25 (3-30 muM) counteracted the inhibitory effects of omega-conotoxin GVIA in field-stimulated rat vas deferens.