Mechanism of presynaptic inhibition of cholinergic transmission in guinea-pig ileum by adenine nucleotides

Abstract

This study was designed to determine the mechanism of action of 2'-, 3'- and 5'-substituted adenine nucleotides on cholinergic transmission in guinea-pig ileum. Segments of ileum were continuously stimulated at 0.2 Hz and IC50 values of nucleotides for inhibition of twitch responses determined. All the nucleotides studied inhibited transmission, the effect being antagonised by 30 X 10(-6) M theophylline. The inhibitors of nucleoside transport, HNBTGR and dipyridamole, potentiated responses to all the nucleotides. Addition of adenosine deaminase reduced responses only to adenosine and 5'-AMP, while inhibition of adenosine deaminase with deoxycoformycin potentiated responses only to 5'-AMP and 5'-ADP. It was concluded that all the nucleotides studied inhibit cholinergic transmission through an action at P1-purinoceptors. However, it was not possible from this study to conclude whether these actions were direct or indirect following their hydrolysis to adenosine.