Effects of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, adenosine, and of oxotremorine and 3-isobutyl-1-methylxanthine on the electrically evoked [3H]acetylcholine secretion in the guinea-pig ileum myenteric plexus.
The guinea-pig ileum longitudinal muscle-myenteric plexus preparation, pre-incubated with [3H]choline, was mounted in an organ bath and superfused with Tyrode's solution. [3H]Acetylcholine secretion was evoked by 150 electrical shocks at 0.5 Hz. N6,2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cyclic AMP) enhanced the [3H]acetylcholine secretion in the presence of eserine and the adenosine receptor antagonist 8-phenyltheophylline (10 mumol l-1). Conversely, in the absence of 8-phenyltheophylline the [3H]acetylcholine secretion was reduced by dibutyryl cyclic AMP. In the absence and presence of 8-phenyltheophylline (apparent KD = 12 mumol l-1), adenosine reduced the [3H]acetylcholine secretion to 33% of control (IC50 = 8 mumol l-1) and to 48% of control (IC50 = 14 mumol l-1) respectively. Neither butyrate, dibutyryl cyclic GMP nor guanosine altered the [3H]acetylcholine secretion. Interaction experiments with 3-isobutyl-1-methylxanthine and oxotremorine were done in the absence of eserine, i.e. when oxotremorine is effective. Oxotremorine depressed the fractional secretion of [3H]acetylcholine with a 'maximal inhibition' of 13% of control (IC50 = 10 nmol l-1). In the presence of 3-isobutyl-1-methylxanthine (5 mmol l-1) oxotremorine depressed the secretion to 2% of control with an apparent IC50 value of 0.9 mumol l-1. 3-Isobutyl-I-methylxanthine (0.01-4 mmol l-1) enhanced the fractional secretion of [3H]acetylcholine with a 'maximal enhancement' value of 232% of control (EC50 = 0.19 mmol l-1). The presence of oxotremorine (30 nmol l-1) counteracted, and higher concentrations reversed, the enhancement caused by 3-isobutyl-1-methylxanthine.(ABSTRACT TRUNCATED AT 250 WORDS)
Alberts
P
P
Division of Experimental Medicine, Swedish Defence Research Establishment, Umeå.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000294:innervation; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives*
D011976:Receptors, Muscarinic; D010095:Oxotremorine; D003994:Bucladesine; D010830:Physostigmine; D013806:Theophylline; D000241:Adenosine; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine