CONTINUOUS MONITORING OF C-13-AMINOPYRINE METABOLISM IN RATS - EFFECTS OF COLD-EXPOSURE AND NORADRENALINE

A system was developed to allow constant monitoring of hepatic cytochr ome P450 activity in awake and unrestrained rats. A continuous C-13-am inopyrine perfusion was performed, and breath samples obtained for end ogenous CO2 production and C-13 measurements, to calculate (CO2)-C-13 production due to aminopyrine demethylation. increasing doses of C-13- aminopyrine produced a hyperbolic increase of expired (CO2)-C-13, comp atible with an in vivo measurement of enzymatic activity. Acute-cold e xposure of the rats during C-13-aminopyrine perfusion produced a two-f old increase of endogenous CO2 production, together with a 27% increas ed C-13-aminopyrine metabolism (p<0.05 vs basal conditions). In contra st, noradrenaline (20 mu g/kg BW/min), despite a similar effect on ene rgy expenditure, did not significantly change C-13-aminopyrine metabol ism. Acute-cold exposure is known to stimulate both adrenal catecholam ine secretion and the sympathetic nervous system. The observed differe nce in C-13-aminopyrine demethylation during cold exposure and noradre naline perfusion, therefore, could be due to a more specific effect of adrenal catecholamines on liver aminopyrine metabolism. These results suggest the possibility of prolonged in vivo monitoring of liver meta bolism pathways such as aminopyrine demethylation, thus allowing the s tudy of drug acute interactions with the cytochrome P450 system.