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Calcium modulatory properties of 2,6‐dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations
Author(s) -
Pirisino R.,
Banchelli G.,
Ignesti G.,
Mantelli L.,
Matucci R.,
Raimondi L.,
Buffoni F.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13726.x
Subject(s) - vas deferens , nitrendipine , medicine , chronotropic , endocrinology , verapamil , reserpine , calcium , ryanodine receptor , voltage dependent calcium channel , tetrodotoxin , chemistry , biology , heart rate , blood pressure
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, 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. 3 In the same tissue, the increase in 45 Ca 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. La 3+ was inactive while nifedipine was a weak inhibitor. By contrast Ni 2+ and Mn 2+ ions were good inhibitors (IC 50 < 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 [ 3 H]‐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 μ m ) counteracted the inhibitory effects of ω‐conotoxin GVIA in field‐stimulated rat vas deferens.