On the nature of endogenous purines modulating cholinergic neurotransmission in the guinea-pig ileum.

Abstract

By means of agonist and enzyme experiments, the relative importance of endogenous adenosine, adenine nucleotides or other purines as modulators of cholinergic neuroeffector transmission in preparations of guinea-pig ileum muscle has been examined. Adenosine, 2-chloroadenosine, AMP, ADP, ATP and AMPPNP reversibly inhibited contractile responses to transmural stimulation of the guinea-pig ileum longitudinal muscle. 5'-adenylate deaminase dose-dependently antagonized the inhibitory effect of adenosine, AMP, ADP, ATP and AMPPNP, but not that of 2-chloroadenosine. 8-p-sulphophenyltheophylline, adenosine deaminase and 5'-adenylate deaminase enhanced contractile responses to transmural nerve stimulation. Adenosine deaminase and 5'-adenylate deaminase were virtually equiactive whereas 8-p-sulphophenyltheophylline was much more effective, and the theophylline derivative also enhanced contractile responses in preparations pretreated with adenosine deaminase or 5'-adenylate deaminase. Moreover, 8-p-sulphophenyltheophylline abolished the inhibition by dipyridamole, whereas adenosine deaminase and 5'-adenylate deaminase only partly antagonized the inhibitory effect of dipyridamole. Application of 5'-adenylate deaminase did not enhance the nerve-induced contractions in preparations pretreated with adenosine deaminase or a combination of dipyridamole and adenosine deaminase. In conclusion, adenosine deaminase and 5'-adenylate deaminase enhanced the nerve-induced contractions in the ileum, and, since 5'-adenylate deaminase was inactive after pretreatment with adenosine deaminase, this suggests that endogenous adenosine rather than 5'-adenine nucleotides modulated cholinergic neurotransmission in the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)