P2X7 receptors contribute to the currents induced by ATP in guinea pig intestinal myenteric neurons

The whole-cell configuration, several pharmacological tools, and single-cell RT-PCR were used to investigate the contribution of P2X7 subunits to the ATP-induced currents (I-ATP) in guinea pig myenteric neurons. I-ATP was recorded in the great majority of tested neurons. ATP concentration-response curve (0.01-10 mM) showed two phases, the first mediated by high-sensitive P2X receptors (hsP2X receptors), observed between 0.01-0.3 mM and the second mediated by low-sensitive P2X receptors (lsP2X receptors). The calculated EC50 values of these phases were 38 and 1759 mu M, respectively. 2'-3'-O-(4-benzoylbenzoyl)-ATP (BzATP) concentration-response curve was monophasic (0.01-1 mM), and less potent (EC50 142 mu M) than ATP to activate hsP2X receptors. A strong inward rectification was noticed when hsP2X receptors were activated with ATP (0.1 mM) and for BzATP-induced currents (0.1 mM; I-BzATP) but a significant lower rectification was noticed when IsP2X receptors were activated (5 mM). Brilliant blue G (BBG) at a concentration of 0.3 mu M (known to inhibit only P2X7 receptors) reduced Imp when IsP2X receptors contributed to it but neither affect hsP2X receptors nor I-BzATP. However, hsP2X receptors and I-BzATP were both inhibited by concentrations >= 1 mu M of this antagonist. BzATP inhibited hsP2X receptors and therefore, it behaves as partial agonist on these receptors. Using the single-cell RT-PCR technique P2X7 mRNA was detectable in 7 out of 13 myenteric neurons exhibiting P2X2 mRNA. Altogether, our results show that low-sensitive P2X receptors are likely P2X7, whereas, the high-sensitive P2X channels are probably constituted, at least in part, by P2X2 subunits. (C) 2011 Elsevier B.V. All rights reserved.