Calcium modulatory properties of 2,6‐dibutylbenzylamine (B25) in rat isolated vas deferens, cardiac and smooth muscle preparations

Abstract

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 bellshaped, 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, a-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 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). 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 < 10-4M), suggesting that a possible opening of T-type VSCC underlies the rhythmic effect of B25. 5 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. 6 B25 (3-30 pLM) counteracted the inhibitory effects of c-conotoxin GVIA in field-stimulated rat vas deferens.

Methylamine and benzylamine induced hypophagia in mice: Modulation by semicarbazide‐sensitive benzylamine oxidase inhibitors and aODN towards Kv1.1 channels

“…Recently, this view has received some indirect experimental support from the observation that, when administered i.p., BZ displays a novel central hypophagic activity in mice only after pretreatment with the Bz-SSAO inhibitors B24 or MDL 72274. We have also observed that BZ induces its e ects probably by acting like the potassium channel blockers TEA or 4-aminopyridine (Pirisino et al, 1993;Banchelli et al, 2000;2001). In other investigations, it has been found that potassium channel blockers reduce food intake in mice by acting as depolarizing compounds in the brain.…”

Pharmacological implications of the Ca2+/cAMP signaling interaction: from risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders

“…; Rae and Calixto ; Pirisino et al. ). We try to explain this fact in Figure , where two components associated with L‐type VACCs blockers are shown: the component of channel (fast activity) and the component of signaling pathway (slow activity).…”

Selective inhibition of amine oxidases differently potentiate the hypophagic effect of benzylamine in mice

“…In their activity, they resemble the indirectly acting compound, amphetamine, or the K q channel blocker, tetra-Ž ethylammonium Pirisino et al, 1993;Banchelli et al, . 2000 .…”