Evidence that the intracellular effects of adenosine in the guinea-pig aorta are mediated by inosine.
Previous studies have demonstrated that high concentrations of adenosine interact with both a cell surface receptor and with an intracellular site to evoke relaxation of the guinea-pig aorta. The intracellular action of adenosine was investigated in the present study. The purine sensitive 'P-site' did not appear to be involved since other P-site agonists did not consistently evoke relaxation. A major interaction with intracellular S-adenosylhomocysteine hydrolase also appeared unlikely since 1-homocysteine had only minor effects on adenosine-evoked responses. Inhibition of adenosine deaminase attenuated responses evoked by high concentrations of adenosine. The deaminated metabolite of adenosine, inosine, also evoked aortic relaxation. These responses were mediated solely via an intracellular site since they were blocked by an inhibitor of nucleoside-facilitated diffusion but were unaffected by an adenosine receptor antagonist. These results indicate that a major part of the intracellular effect of adenosine is mediated by its deaminated metabolite inosine.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
C042902:(2'-5')-9-xylofuranosyladenine trimer; D013868:Thioinosine; D007288:Inosine; D013806:Theophylline; C028322:8-phenyltheophylline; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D009638:Norepinephrine