Elicitation of supramaximal thermogenesis by aminophylline in the rat.
Previous studies in rats indicate that maximal thermogenesis during severe cold exposure is suppressed by overnight fasting. Since fasting depresses sympathetic activity and the activity of adrenergic receptors, both of which affect substrate mobilization in cold, the present study attempted to restore maximal thermogenesis in fasted rats by exogenous sympathomimetics and a hypoxanthine (aminophylline). In overnight-fasted rats, exogenous sympathomimetics had no effect in further enhancing maximal thermogenesis induced by exposure to severe cold (in He-O2 at -10 degrees C), indicating maximization of endogenous sympathetic discharge and saturation of adrenergic receptor binding during severe cold exposure. In contrast, aminophylline (1.25-37.5 mg/kg ip) elicited "supramaximal thermogenesis" beyond control maximums in both fasted (+19.4%) and fed +14.4%) conditions in a dose-dependent manner, resulting in improved cold tolerance and prevention of hypothermia. Since aminophylline acts distally to adrenergic receptors to increase intracellular adenosine 3',5'-cyclic monophosphate concentration, it is possible that such increases could enhance substrate mobilization to support supramaximal thermogenesis in severe cold.
D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D003080:Cold Temperature; D004837:Epinephrine / Q000494:pharmacology; D005215:Fasting; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000628:Aminophylline; D008729:Methoxamine; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine