Spanish 
Chinese 
Russian 
German 
French 
Japanese 
Portuguese 
Hindi Research Article
Histamine Modulates Isoproterenol Efficacy at the β2 Adrenoceptor: Inferences Regarding Allosteric Modulation by Imidazole-Containing Compounds
| Marvin A Soriano-Ursúa1*, Daniel McNaught-Flores2, José Correa-Basurto3,4, José A Arias-Montaño2 and José G Trujillo-Ferrara3,4 | |
| 1Departamento de Fisiología y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México | |
| 2Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, Av. Instituto Politécnico Nacional, México | |
| 3Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, México | |
| 4Laboratorio de Modelado Molecular y Bioinformática de la Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México | |
| *Corresponding Author : | Marvin A Soriano-Ursúa Departamento de Fisiología. Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón, C.P. 11340, México D.F Tel: (052)57296000 Extn.62747 Fax: (052)57296000 Extn.62745 E-mail: msoriano@ipn.mx |
| Received July 19, 2013; Accepted August 16, 2013; Published August 19, 2013 | |
| Citation: Soriano-Ursúa MA, McNaught-Flores D, Correa-Basurto J, Arias-Montaño JA, Trujillo-Ferrara JG (2013) Histamine Modulates Isoproterenol Efficacy at the β2 Adrenoceptor: Inferences Regarding Allosteric Modulation by Imidazole-Containing Compounds. Biochem Physiol 2:114. doi:10.4172/2168-9652.1000114 | |
| Copyright: © 2013 Soriano-Ursúa MA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
Abstract
In the last few years, evidence has been mounting of the possible allosteric modulation of second messenger formation on β2-adrenoceptors (β2ARs) induced by non-arylethylamine compounds. We herein addressed this issue by carrying out functional and molecular modeling studies to explore the possibility that imidazole-containing compounds (ICCs) affect the formation and accumulation of cAMP by mediating β2AR activation. Results show that histamine (an ICC) had no effect on basal cAMP accumulation in COS-7 cells transfected with the human β2AR (10.4 ± 1.1 pmol/mg protein), but significantly augmented the receptor response to the agonist isoproterenol (137 ± 7% of controls, EC50 10.5 μM, pEC50 5.87 ± 0.06). Moreover, histamine (10 μM) did not affect the isoproterenol inhibition of 3H]-dihydroalprenolol binding to hβ2ARs in membranes of transfected COS-7 cells. Q-site Finder program and molecular docking studies identified possible sites of interaction for ICCs on the β2AR, but the estimated affinities were lower than those reported for well-known β2AR ligands on the orthosteric site. On the basis of the present experimental and theoretical data, we postulate that direct ICC-hβ2AR interactions can allosterically modulate agonist-induced receptor activation. Implications of these findings for drug design are discussed.
