EFFECTS OF 5-METHYLPYRAZOLE-3-CARBOXYLIC ACID (U-19425) AND NICOTINIC ACID ON LIPOLYSIS IN VITRO AND IN VIVO AND ON CYCLIC-3',5'-AMP PHOSPHODIESTERASE

¹ Metabolic Diseases Research, The Upjohn Company, Kalamazoo, Michigan

Inhibition of epinephrine-stimulated lipolysis in vitro by U-19425 and nicotinic acid at concentrations of 10^-6, 10^-5 and 10^-4 M was equivalent at each dose. Oral administration of U-19425 (25 mg/kg) and nicotinic acid (100 mg/kg) to fed rats depressed plasma free fatty acid concentrations, lowered free fatty acid concentration in adipose tissue and inhibited basal lipolysis in vitro. The reduced concentration of free fatty acids in incubation medium and adipose tissue was shown not to be the result of enhanced reesterification. U-19425 also inhibited basal and theophylline-stimulated lipolysis in vitro, but failed to inhibit lipolysis stimulated by dibutyryl cyclic 3',5'-AMP. Neither U-19425 nor nicotinic acid affected the hydrolysis of cyclic 3',5'-AMP by the phosphodiesterase.