alexa Histamine Modulates Isoproterenol Efficacy at the and#946;2 Adrenoceptor: Inferences Regarding Allosteric Modulation by Imidazole-Containing Compounds | OMICS International | Abstract
ISSN: 2168-9652

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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: [email protected]
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.

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