EPIDERMAL GROWTH-FACTOR MODULATES THE LIPOLYTIC ACTION OF CATECHOLAMINES IN RAT ADIPOCYTES - INVOLVEMENT OF A GI-PROTEIN

In isolated adipocytes, epidermal growth factor (EGF) did not affect b asal (nonstimulated) lipolysis, but interfered with the lipolytic acti on of isoproterenol (ISO) or glucagon. Similarly, EGF did not affect b asal levels of cyclic AMP but interfered with the signal generated by ISO. However, EGF did not affect lipolysis stimulated by forskolin or cyclic AMP analogues. These results suggest that EGF interfered with t he signal transduction between lipolytic hormone receptors and adenyla te cyclase. To determine whether EGF was activating a G(i) protein, ad enosine deaminase (ADA) was added to degrade endogenously released ade nosine. While the nonmetabolizable adenosine analogue N6-(phenylisopro pyl)adenosine (PIA) inhibited ADA-stimulated lipolysis, EGF affected n either ADA-stimulated lipolysis nor the dose-response curve for PIA. H owever, EGF did not affect ISO-stimulated lipolysis in pertussis toxin -treated cells. Similarly, in the presence of ADA, the effects of ISO on lipolysis and on cyclic AMP levels were not affected by EGF. The ad dition of PIA restored the effect of EGF on both lipolysis and cyclic AMP. Since EGF decreased the IC50 for the inhibitory effect of PIA on (ISO + ADA)-stimulated lipolysis, we suggest that EGF modulates the in teraction between G(s) and G(i) in the control of adenylate cyclase.