Indirect evidence against a contribution of the guanine nucleotide-binding inhibitory component of adenylate cyclase to impaired lipolysis in the epididymal adipose tissue of congenitally obese (ob/ob) mice.

The mixed adrenergic agonist epinephrine, at a 10 microM concentration, stimulated cyclic AMP production and glycerol release in the epididymal adipose tissue of ob/ob male mice. These effects when tested, respectively, after 7 min in the presence and after 60 min in the absence of theophylline were, however, 7- and 5-fold lower than in lean controls. The alpha-adrenergic blocker phentolamine and adenosine deaminase (which destroys extracellular adenosine) did not restore a normal lipolytic response to epinephrine in the adipose tissue of ob/ob mice. These data provide indirect evidence against a hyperactive mechanism in the coupling of alpha-adrenergic receptors and adenosine receptors to Ni, the guanine nucleotide-binding inhibitory component of adenylate cyclase, as the cause of reduced lipolysis in the adipose tissue of ob/ob mice.