Article date: August 1993
By: R. Pirisino, G. Banchelli, G. Ignesti, L. Mantelli, R. Matucci, L. Raimondi, F. Buffoni, in Volume 109, Issue 4, pages 1038-1045
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.
Experiments with tetrodotoxin, reserpine, capsaicin, α‐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.
In the same tissue, the increase in 45Ca2+ 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).
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 < 10−4m), suggesting that a possible opening of T‐type VSCC underlies the rhythmic effect of B25.
In radioligand binding studies competition experiments with [3H]‐nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine‐sensitive binding sites of heart and vas deferens smooth muscle.
B25 (3–30 μm) counteracted the inhibitory effects of ω‐conotoxin GVIA in field‐stimulated rat vas deferens.
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.
Experiments with tetrodotoxin, reserpine, capsaicin, α‐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.
In the same tissue, the increase in 45Ca2+ 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).
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 < 10−4m), suggesting that a possible opening of T‐type VSCC underlies the rhythmic effect of B25.
In radioligand binding studies competition experiments with [3H]‐nitrendipine indicated that only at high concentrations was B25 able to interact with dihydropyridine‐sensitive binding sites of heart and vas deferens smooth muscle.
B25 (3–30 μm) counteracted the inhibitory effects of ω‐conotoxin GVIA in field‐stimulated rat vas deferens.
DOI: 10.1111/j.1476-5381.1993.tb13726.x
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