On the nature of endogenous purines modulating cholinergic neurotransmission in the guinea-pig ileum.
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)
Wiklund
N P
NP
Department of Physiology, Karolinska Institute, Stockholm, Sweden.
Gustafsson
L E
LE
D000659:AMP Deaminase / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D000227:Adenine Nucleotides; D011687:Purines; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000243:Adenosine Deaminase; D000659:AMP Deaminase; D000241:Adenosine