Peripheral and central actions of AF64A (ethylcholine mustard aziridinium ion) on acetylcholine release, in vitro: Comparison with hemicholinium

Abstract

The acute effects of ethylcholine mustard aziridinium ion (AF64A) and hemicholinium-3 (HC-3) on the release of endogenous acetylcholine (ACh) from isolated tissues were examined. Whereas addition of HC-3 (10(?6)-10(?5) M) significantly reduced the output of ACh from isolated guinea-pig ileum longitudinal muscle strip elicited by 10 Hz stimulation, AF64A had no effect and even enhanced the release of radiolabel elicited by 1 Hz stimulation when this tissue was pre-loaded with [(3)H]choline. Similarly, HC-3 (10(?5) M) reduced ouabain-induced endogenous ACh release from isolated rat hippocampus. Addition of AF64A (10(?5)?5 x 10(?5) M) caused a slight increase in ACh release. In isolated rat cortex, however, AF64A did not affect ACh release. Moreover, AF64A caused a decrease in ouabain-stimulated ACh release from striatum. The present study indicates that: (a) the in vitro actions of AF64A differ from those of HC-3 and (b) the acute effects of AF64A on endogenous ACh release vary, depending on the tissues studied and the stimulation parameters used.