(−)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries

Abstract

Previous findings enable us to hypothesize that (−)-α-bisabolol acts as inhibitor of voltage-dependent Ca2+ channels in smooth muscle. The current study was aimed at consolidating such hypothesis through the recording of isometric tension, measurement of intracellular Ca2+ as well as discovery of channel target using in silico analysis. In rat aortic rings, (−)-α-bisabolol (1–1000µM) relaxed KCl- and phenylephrine-elicited contractions, but the IC50 differed significantly (22.8 [17.6–27.7] and 200.7 [120.4–334.6] µM, respectively). The relaxation of phenylephrine contractions remained unaffected by l-NAME, indomethacin, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, tetraethylammonium, glibenclamide or KT-5720. Under Ca2+-free conditions, (−)-α-bisabolol did not alter the contractions evoked by phenylephrine or caffeine whereas it reduced those evoked by CaCl2 in KCl-, but not in PHE-stimulated preparations. Furthermore, it did not significantly alter the contractions evoked by phorbol 12,13-dibutyrate or induced by the extracellular Ca2+ restoration in cyclopiazonic acid-treated preparations. In mesenteric rings loaded with Fluo-4 AM, (−)-α-bisabolol blunted the tension and the cytosolic levels of Ca2+ in response to K+ but not to norepinephrine. Silico docking analysis of the Cavβ2a subunit of voltage-dependent Ca2+ channel indicated putative docking sites for (−)-α-bisabolol. These findings reinforce the ability of (−)-α-bisabolol to inhibit preferentially contractile responses evoked by Ca2+ influx through voltage-dependent Ca2+ channels.