5-aminoimidazole-4-carboxamide riboside administration and purine release from the hypoxic/hypotensive rat cerebral cortex

The effects of the purine precursor 5-aminoimidazole-4-carboxamide riboside (AICAriboside) on the release of purines from cerebral cortices of normoxic and hypoxic/hypotensive rats was studied with the cortical cup technique. AICAriboside was administered either intravascularly (50 mg/kg) or intraperitoneally (500 mg/kg) to ascertain whether this agent can be used to enhance adenosine levels in the cerebral cortical interstitial fluid. Following its intraperitoneal administration AICAriboside appeared rapidly in the cortical superfusates at concentrations of up to 9 μM and remained at this level for a 90 min period. After intravascular administration, AICAriboside levels peaked at 2 μM, and then declined rapidly. No increases in basal (normoxic) or hypoxia-elicited adenosine levels in the cortical superfusates were observed. Increases did occur in the basal and hypoxia-evoked levels of hypoxanthine, xanthine and, especially, of uric acid. AICAriboside administration appears to have caused an increase in adenosine metabolite, rather than in adenosine, levels in the cerebral interstitial fluid and it may therefore be of little benefit as a precursor for adenosine formation and release in the treatment of cerebral ischemic damage.