Interaction of forskolin with the effect of atropine on [3H]acetylcholine secretion in guinea-pig ileum myenteric plexus.
1. Secretion of [3H]acetylcholine was studied in the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. The transmitter stores of the cholinergic nerves were labelled by pre-incubation with [3H]choline. The preparation was mounted in an organ bath and superfused with Tyrode solution containing hemicholinium-3 and eserine. [3H]Acetylcholine secretion was evoked by electrical stimulation (0.5 Hz, 150 shocks). 2. 8-Bromo cyclic AMP, the adenylate cyclase activator forskolin, and the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine enhanced the [3H]acetylcholine secretion in a concentration-dependent manner. The values of 'maximal enhancement' calculated were similar, viz. 200-300% of control. 3. 8-Bromo cyclic GMP reduced the [3H]acetylcholine secretion. 4. The 'maximal enhancement' of 3-isobutyl-1-methylxanthine was not altered by the presence of forskolin (25 mumol/l) suggesting a common mechanism of action, i.e. elevation of endogenous cyclic AMP levels. 5. The muscarinic acetylcholine receptor antagonist atropine enhanced the [3H]acetylcholine secretion with a 'maximal enhancement' of 506% of control. Presence of neither forskolin (25 mumol/l) nor 3-isobutyl-1-methylxanthine (5 mmol/l) altered the 'maximal enhancement' for atropine. 6. In contrast, atropine (1 mumol/l) and 4-aminopyridine (0.5 mmol/l) additively enhanced the [3H]acetylcholine secretion. 7. The results suggest that neuronal cyclic AMP may be involved in muscarinic acetylcholine receptor-mediated control of [3H]acetylcholine secretion in guinea-pig ileum myenteric plexus.
Alberts
P
P
Division of Experimental Medicine, National Defence Research Institute, Umeå, Sweden.
Ogren
V R
VR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015761:4-Aminopyridine; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects
D000631:Aminopyridines; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D001285:Atropine; D015761:4-Aminopyridine; D006152:Cyclic GMP; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine