Stimulation of acetylcholine release from guinea-pig ileal synaptosomes by cyclic nucleotides and forskolin.
Various agents which are known to affect intracellular levels of cAMP have been assessed for their ability to induce the release of [3H]acetylcholine ([3H]ACH) from a synaptosomal preparation derived from the guinea-pig ileum myenteric plexus. 8-Bromo-cAMP increased the release of [3H]ACh above basal levels. While 8-bromo-cGMP also increased the release, this nucleotide was far less potent than 8-bromo-cAMP. Comparison of the release caused by the cyclic nucleotides to the release induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP) suggested that there is some relationship, as yet undefined, between the 8-bromo-cAMP-induced and the DMPP-induced release, while no relationship was evident between the release induced by 8-bromo-cGMP and that caused by DMPP. The 8-bromo-cAMP-induced release was Ca2+-dependent. Neither adenosine, clonidine, nor oxotremorine (all of which modulate the nicotinically-induced release) affected the 8-bromo-cAMP-induced release. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine stimulated the release of [3H]ACh as did the adenylate cyclase activator forskolin. The forskolin-induced release was not affected by adenosine, clonidine or oxotremorine. The ability of the modulators to block the nicotinically-induced release but not the release caused by the cyclic nucleotides indicates that the modulation of release evoked by nicotinic activity does not occur at a step involving protein phosphorylation.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium
D000959:Antihypertensive Agents; D004224:Diterpenes; D009712:Nucleotides, Cyclic; D014316:Tritium; D005576:Colforsin; D004246:Dimethylphenylpiperazinium Iodide; D000109:Acetylcholine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine