5-Amino-4-imidazolecarboxamide riboside raises adenosine in perfused hypoxic rat heart.
The effects of 5-amino-4-imidazolecarboxamide riboside (rAICA) on coronary adenosine efflux were examined in blood-free perfused working rat heart preparations subjected to mild (70% O2) and severe hypoxia (45% O2). Under these hypoxic conditions, no significant increase of coronary adenosine effluxes was observed in the presence of 300 microM rAICA alone. However, rAICA-induced augmentation of coronary adenosine efflux during hypoxia was revealed in the presence of an adenosine deaminase inhibitor, erythro-(2-hydroxy-3-nonyl)adenine hydrochloride, indicating that the failure to note the increase in coronary adenosine efflux was due to a rapid deamination of adenosine to inosine. A depression in heart rate during mild and severe hypoxia was significantly exacerbated by rAICA. These effects on heart rate were mediated by adenosine, since they were effectively blocked by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine, a selective adenosine A1-receptor antagonist. These results suggest that rAICA elevates adenosine efflux during hypoxia.
Oei
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Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
Burrier
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AC
Jeng
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D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology*; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012263:Ribonucleosides / Q000494:pharmacology*
D058892:Adenosine Deaminase Inhibitors; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; C010192:9-(2-hydroxy-3-nonyl)adenine; D007288:Inosine; D000225:Adenine; D000241:Adenosine