Metabolic responses of perfused rat livers to alpha- and beta-adrenergic agonists, glucagon and cyclic AMP.
1. The mechanism of action of glucagon and epinephrine was studied in perfused rat livers. Hormone-induced transitions from one metabolic steady state to another were followed in a non-recirculating perfusion system. Glucose and lactate production rates, oxygen uptake and K+ redistribution were measured. 2. Glucagon (3 nM), cyclic AMP (0.2 mM) and epinephrine (0.5 muM) had similar effects on K+ concentrations in the perfusate. Glycogenolysis responded more rapidly and O2 uptake was enhanced to a larger extent with epinephrine than with the other agents. alpha- and beta-receptor responses were differentiated by the use of phenylephrine (0.5 muM), isoproterenol (0.5 muM) and adrenergic blocking agents (phentolamine and beta-blocker Ro 3-4787 at 0.1 mM). 3. alpha-receptors mediated an activation of glucose production that was very rapid and was paralleled by a transient decrease of K+ concentrations in the effluent from the liver, lactate production rose gradually. Respiration was also enhanced, but fell again as lactate production increased. 4. beta-receptor stimulation was followed by an increase of glucose production that was less drastic and was paralleled by a K+ release, lactate production and respiration were only slightly enhanced. beta stimulation and glucagon both resulted in an inhibition of the alpha-adrenergic effect on lactate release and simultaneously increased O2 uptake. 5. We concluded that in perfused rat livers alpha- as well as beta-adrenergic receptor stimulation resulted in an activation of glycogenolysis, possibly by two different mechanisms.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D001572:Benzofurans; D004983:Ethanolamines; D011941:Receptors, Adrenergic; D010656:Phenylephrine; C010831:bufuralol; D006003:Glycogen; D005934:Glucagon; D000242:Cyclic AMP; D007545:Isoproterenol; D011188:Potassium; D004837:Epinephrine; D010646:Phentolamine