Inhibition of nerve-mediated contractions in isolated guinea-pig ileum by 1-methylisoguanosine, a novel purine from a sponge.
1-Methylisoguanosine, a novel purine isolated from the sponge Tedania digitata (Schmidt) selectively inhibited contractions produced by nerve stimulation in the guinea-pig ileum but was without effect on contractions produced by acetylcholine or histamine. The ED50 for inhibition of nicotine responses or responses to submaximal transmural stimulation was 1.1 mumoles/l. The inhibition of nerve-mediated contractions appeared to be due to inhibition of transmitter release from nerve endings in the ileum, as has been suggested for the action of adenosine. Theophylline antagonized the action of 1-methylisoguanosine and overall the results suggest that 1-methyl-isoguanosine acts at an adenosine receptor in the guinea-pig ileum, but is approximately ten times more potent than adenosine itself. A series of related purines which were resistant to the action of adenosine deaminase were also tested for their effect on the nerve-mediated contractions of guinea-pig ileum and the results compared with the in vivo effect on muscle relaxation in mice. All active purines tested produced results qualitatively similar to those of 1-methylisoguanosine itself.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D011161:Porifera / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D013806:Theophylline / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D006151:Guanosine; C022591:doridosine; D013806:Theophylline; D000241:Adenosine