(-)-α-Bisabolol inhibits preferentially electromechanical coupling on rat isolated arteries
| Autor: | Pjc Magalhães, Alfredo Augusto Vasconcelos-Silva, Saad Lahlou, Walter B.S. Freire, R. J. B. de Siqueira, Helder Veras Ribeiro-Filho, R.S. Freire, F. Cosker, M.A. Soares |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Vascular smooth muscle Physiology Calcium in biology Potassium Chloride Glibenclamide chemistry.chemical_compound Inhibitory Concentration 50 Phenylephrine Extracellular medicine Animals Computer Simulation Rats Wistar Bisabolol Aorta Pharmacology Tetraethylammonium Dose-Response Relationship Drug Anatomy Rats Molecular Docking Simulation Monocyclic Sesquiterpenes chemistry Phorbol Biophysics Molecular Medicine Calcium Calcium Channels Sesquiterpenes medicine.drug Muscle Contraction |
| Zdroj: | Vascular pharmacology. 63(1) |
| ISSN: | 1879-3649 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect