Modulation of the release of acetylcholine from ileal synaptosomes by adenosine and adenosine 5'-triphosphate.
Low concentrations of either adenosine or adenosine 5'-triphosphate (ATP) inhibited the nicotinically induced release of [3H]acetylcholine from synaptosomes derived from the guinea-pig ileum myenteric plexus. Adenosine and ATP were equipotent in their ability to inhibit the release and the inhibition was reversible by theophylline in both cases. The data suggest that ATP may have acted after initial hydrolysis to adenosine and that the receptor involved may be the P1 or similar R site receptor. High concentrations of ATP caused marked increases in the release of [3H]acetylcholine. This release was neither temperature- nor calcium-dependent. Because the concentrations required were similar, however, to those which have been reported to cause ATP-induced contractions in intact preparations, further studies of the phenomenon were carried out. Lactate dehydrogenase was not released with the [3H]acetylcholine, suggesting that indiscriminate lysis of the membranes had not occurred. The release was not affected by theophylline, indomethacin, tetrodotoxin or adenosine. The ATP analog, adenylyl (beta, gamma-methylene)-diphosphonate did not cause the increase in release, therefore phosphorylation may be required for the effect. The mechanism of increased release remains to be defined, but the data suggest that it is unlikely that a P2 receptor is involved.
D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D013806:Theophylline / Q000494:pharmacology
D011978:Receptors, Nicotinic; D000255:Adenosine Triphosphate; D013806:Theophylline; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium