Por favor, use este identificador para citar o enlazar este ítem:
https://doi.org10.1124/mol.106.030163
Twittear
Título: | Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP |
Otros títulos: | Different sites for ATP and BzATP at P2X7 receptors |
Fecha de publicación: | 2007 |
Editorial: | American Society for Pharmacology and Experimental Therapeutics |
Cita bibliográfica: | Molecular Pharmacology, volumen 71, nº 1, año 2007, páginas: 92-100. |
Materias relacionadas: | CDU::6 - Ciencias aplicadas |
Palabras clave: | P2X7 ATP Canal iónico |
Resumen: | Agonist properties of the P2X7 receptor (P2X7R) differ strikingly from other P2X receptors in two main ways: high concentrations of ATP (> 100 microM) are required to activate the receptor, and the ATP analog 2',3'-O-(4-benzoyl-benzoyl)ATP (BzATP) is both more potent than ATP and evokes a higher maximum current. However, there are striking species differences in these properties. We sought to exploit the large differences in ATP and BzATP responses between rat and mouse P2X7R to delineate regions or specific residues that may be responsible for the unique actions of these agonists at the P2X7R. We measured membrane currents in response to ATP and BzATP at wild-type rat and mouse P2X7R, at chimeric P2X7Rs, and at mouse P2X7Rs bearing point mutations. Wild-type rat P2X7R was 10 times more sensitive to ATP and 100 times more sensitive to BzATP than wild-type mouse P2X7R. We found that agonist EC50 values were determined solely by the ectodomain of the P2X7R. Two segments (residues 115-136 and 282-288), when transposed together, converted mouse sensitivities to those of rat. Point mutations through these regions revealed a single residue, asparagine284, in the rat P2X7R that fully accounted for the 10-fold difference in ATP sensitivity, whereas the 100-fold difference in BzATP sensitivity required the transfer of both Lys127 and Asn284 from rat to mouse. Thus, single amino acid differences between species can account for large changes in agonist effectiveness and differentiate between the two widely used agonists at P2X7 receptors. |
Autor/es principal/es: | Young, Mark T. Pelegrin, Pablo Surprenant, Annmarie |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular B e Inmunología |
Versión del editor: | https://molpharm.aspetjournals.org/content/71/1/92.long |
URI: | http://hdl.handle.net/10201/138129 |
DOI: | https://doi.org10.1124/mol.106.030163 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 25 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Descripción: | ©2007. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted, version of a Published Work that appeared in final form in Molecular Pharmacology,. To access the final edited and published work see https://doi.org10.1124/mol.106.030163 |
Aparece en las colecciones: | Artículos: Bioquímica y Biología Molecular "B" e Inmunología |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
2007 MolPharm.pdf | Versión aceptada del artículo | 5,06 MB | Adobe PDF | Visualizar/Abrir |
Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons