ATP is a mediator of the fast inhibitory junction potential in human jejunal circular smooth muscle

The neurotransmitter(s) that generates the fast component of the inhibitory junction potential (IJP-F) in human jejunal circular smooth muscle is not known. The aim of this study was to determine the role of ATP and purinergic receptors in the generation of the IJP-F in human jejunal circular smooth muscle strips. The P-2-receptor antagonist suramin (100 mu M) reduced the IJP-F by 28%. Apamin (1 mu M) reduced the IJP-F by 25%. Desensitization of muscle strips with the putative P-2x-receptor agonist alpha,beta-methylene ATP (alpha,beta-MeATP, 100 mu M) decreased the IJP-F by 44%, and desensitization with the putative P-2y-receptor agonist adenosine 5'-O-2-thiodiphosphate (ADP beta S) completely abolished the IJP-F. Desensitization with the putative P-2y-receptor agonist 2-methylthioATP had no effect on the IJP-F. Exogenous ATP evoked a hyperpolarization with a time course that matched the IJP-F. The ATP-evoked hyperpolarization was reduced by apamin and suramin, reduced by desensitization with alpha,beta-MeATP (69% decrease), and abolished by desensitization with ADP beta S. These data suggest that the IJP-F in human jejunal circular smooth muscle is mediated in part by ATP through an ADP beta S-sensitive P-2 receptor.