Effect of N6-(L-2-phenylisopropyl)adenosine and insulin on cAMP metabolism in 3T3-L1 adipocytes

Abstract

The antilipolytic effect of N6-(L-2-phenylisopropyl)-adenosine (PIA), an adenosine analogue thought to act via cell surface receptors, was investigated in 3T3-L1 adipocytes. PIA (1 microM) was as effective as 1 nM insulin in reducing lipolysis stimulated by 1 nM isoproterenol and more effective than insulin at higher isoproterenol concentrations. In intact adipocytes, PIA reduced isoproterenol-induced cyclic AMP (cAMP) accumulation and increased particulate cAMP phosphodiesterase. In particulate preparations PIA suppressed isoproterenol stimulation of adenylate cyclase. PIA was more effective than 5'-N-ethylcarboxamide adenosine (NECA) or adenosine in inhibiting adenylate cyclase and activating phosphodiesterase. In intact adipocytes, two agents with so-called "insulin-like" activities, i.e., anti-insulin receptor antibodies and wheat germ agglutinin (WGA), also increased particulate cAMP phosphodiesterase. Pertussis toxin, which inhibits stimulation of the particulate cAMP phosphodiesterase by insulin (but not by isoproterenol), also inhibited the effects of PIA, anti-insulin receptor antibodies, and WGA. In 3T3-L1 cells, PIA appears to inhibit lipolysis by inhibiting adenylate cyclase and stimulating phosphodiesterase; these effects of PIA, as well as those of anti-insulin receptor antibodies and WGA on phosphodiesterase, may be mediated via guanyl nucleotide-binding proteins.