Isolated Auerbach's plexus-longitudinal muscle preparations from guinea-pig ileum and slices of the rat cerebral cortex have been used to study the effect of adenine nucleotides on the release of acetylcholine. The release of acetylcholine evoked by cholecystokinin was completely inhibited by adenosine. The effect of nucleotides on neuro-effector transmission of electrically stimulated longitudinal muscle strip was also studied. Adenosine and adenosine triphosphate reduced the release of acetylcholine provided a low frequency of stimulation was applied. While the three adenine nucleotides (adenosine mono-, di- and triphosphate) dose-dependently reduced neuro-effector transmission in Auerbach's plexus-longitudinal muscle preparation, adenine, guanosine triphosphate and dibutyryl-cyclic AMP had no effect. Theophylline, an adenosine receptor antagonist, prevented the inhibitory effect of the nucleotides. In addition, theophylline alone enhanced the release of acetylcholine both from Auerbach's plexus and from the nerve terminals of the cortical slice. This indicates that there might be a continuous control of ACh release by an adenine nucleotide. These results are discussed in relation to the release of adenosine triphosphate from purinergic nerves in the intestine and of adenosine from slices of cerebral cortex; the possibility is raised that adenine nucleotides released from nerves might act as a type of presynaptic inhibitory transmitter on cholinergic neurons. Furthermore, if some of the released nucleotide originates from the synaptic vesicles of cholinergic neurons, it might serve as a negative feed-back transmitter for acetylcholine release. The inhibitory effect of adenosine and related nucleotides on the cholecystokinin-induced release of acetylcholine from the gut might be of physiological importance since gastrointestinal polypeptides play a very important role in maintaining gastrointestinal motility.
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