title: (-)-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 Ca(2+) channels in smooth muscle. The current study was aimed at consolidating such hypothesis through the recording of isometric tension, measurement of intracellular Ca(2+) 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 Ca(2+)-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 Ca(2+) restoration in cyclopiazonic acid-treated preparations. In mesenteric rings loaded with Fluo-4 AM, (-)-α-bisabolol blunted the tension and the cytosolic levels of Ca(2+) in response to K(+) but not to norepinephrine. Silico docking analysis of the Cavβ2a subunit of voltage-dependent Ca(2+) channel indicated putative docking sites for (-)-α-bisabolol. These findings reinforce the ability of (-)-α-bisabolol to inhibit preferentially contractile responses evoked by Ca(2+) influx through voltage-dependent Ca(2+) channels.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: rodrigo_siqueira@yahoo.com.br.
authors.forename: R J B
authors.initials: RJ
authors.lastname: de Siqueira
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: H V
authors.initials: HV
authors.lastname: Ribeiro-Filho
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Freire
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Cosker
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: W B S
authors.initials: WB
authors.lastname: Freire
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Vasconcelos-Silva
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Soares
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Lahlou
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: P J C
authors.initials: PJ
authors.lastname: Magalhães
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D062105:Molecular Docking Simulation; D000081222:Monocyclic Sesquiterpenes; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; D010656:Phenylephrine; C004497:bisabolol; D011189:Potassium Chloride; D002118:Calcium
keywords: (−)-α-Bisabolol; Docking analysis; Electromechanical coupling; Intracellular calcium; Vascular smooth muscle