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 basal (nonstimulated) lipolysis, but interfered with the lipolytic action of isoproterenol (ISO) or glucagon. Similarly, EGF did not affect basal 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 the signal transduction between lipolytic hormone receptors and adenylate cyclase. To determine whether EGF was activating a Gi protein, adenosine deaminase (ADA) was added to degrade endogenously released adenosine. While the nonmetabolizable adenosine analogue N6-(phenylisopropyl)adenosine (PIA) inhibited ADA-stimulated lipolysis, EGF affected neither ADA-stimulated lipolysis nor the dose-response curve for PIA. However, 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 addition 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 interaction between GS and Gi in the control of adenylate cyclase.
Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
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Tebar
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Ramírez
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Soley
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives; D004815:Epidermal Growth Factor / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008066:Lipolysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D005576:Colforsin; D004815:Epidermal Growth Factor; D005934:Glucagon; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; D000241:Adenosine; D007545:Isoproterenol