Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP

Young, Mark Thomas, Pelegrin, Pablo and Surprenant, Annmarie 2007. Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Molecular Pharmacology 71 (1) , pp. 92-100. 10.1124/mol.106.030163

Full text not available from this repository.

Abstract

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.

Item Type: Article
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: American Society for Pharmacology and Experimental Therapeutics
ISSN: 0026-895X
Last Modified: 02 May 2019 12:12
URI: http://orca.cf.ac.uk/id/eprint/57838

Citation Data

Cited 71 times in Google Scholar. View in Google Scholar

Cited 79 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item