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

• Published in: Vascular pharmacology 2014-10, Vol.63 (1), p.37-45
• Main Authors: de Siqueira, R.J.B, Ribeiro-Filho, H.V, Freire, R.S, Cosker, F, Freire, W.B.S, Vasconcelos-Silva, A.A, Soares, M.A, Lahlou, S, Magalhães, P.J.C
• Format: Article
• Language: English
• Subjects: (−)-α-Bisabolol; Animals; Aorta - drug effects; Aorta - metabolism; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Cardiovascular; Computer Simulation; Docking analysis; Dose-Response Relationship, Drug; Electromechanical coupling; Inhibitory Concentration 50; Intracellular calcium; Male; Molecular Docking Simulation; Muscle Contraction - drug effects; Phenylephrine - pharmacology; Potassium Chloride - pharmacology; Rats; Rats, Wistar; Sesquiterpenes - administration & dosage; Sesquiterpenes - pharmacology; Vascular smooth muscle
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2014.06.006

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 (1–1000 µM) 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.