DISSOCIATION OF CATECHOLAMINE-INDUCED CALORIGENESIS FROM LIPOLYSIS AND GLYCOGENOLYSIS IN INTACT ANIMALS

¹ Department of Pharmacology, Woman's Medical College of Pennsylvania, Philadelphia, Pennsylvania

The relationship between changes in plasma free fatty acids (FFA), in glucose and in lactic acid and the rise in oxygen consumption produced by sympathomimetic amines was studied in intact, anesthetized dogs and rats. In the dog norepinephrine (NE) and isoproterenol (ISO) (1 µg/kg/min) produced similar rises in plasma FFA, but ISO produced a more marked calorigenesis than did NE. ISO increased plasma glucose and lactic acid, whereas NE did not. In the dog MJ 1999 completely inhibited NE-induced lipolysis and calorigenesis; whereas in the rat, with epinephrine (E) as the agonist, MJ 1999 prevented the rise in lactic acid and only reduced the rise in glucose and in oxygen consumption, but MJ 1999 did not inhibit the rise in FFA. Nicotinic acid suppressed the rise in FFA regularly produced by ISO in the dog and by E in the rat; but nicotinic acid had little effect on the rise in glucose, in lactic acid or in oxygen consumption. In the rat dihydroergotamine also completely inhibited the rise in FFA, reduced the rise in glucose but had no significant effect on the rise in oxygen consumption or in lactic acid in response to E. In the rat the combination of MJ 1999 plus nicotinic acid completely inhibited the rise in all three plasma substrates regularly produced by E, but this combination of agents only reduced the rise in oxygen consumption. A possible supportive, rather than causative, role of FFA, lactic acid and glucose in catecholamine-induced calorigenesis is discussed. Since selective antagonists of catecholamine effects differentially influence the increase in FFA and the calorigenic effect, the rise in FFA does not appear to be the cause of the increased oxygen consumption.