Protein kinase C attenuates beta-adrenergic receptor-mediated lipolysis, probably through inhibition of the beta1-adrenergic receptor system.
Lipolysis in rat white adipocytes is stimulated by beta-adrenergic agonists. Phorbol 12-myristate 13-acetate (PMA) attenuated the receptor-mediated lipolysis by causing a shift of the dose-response curve to the higher concentrations of norepinephrine and isoproterenol. Although the adipocytes possess beta1-, beta2-, and beta3-adrenergic receptor subtypes, the effect of PMA was observed only when a beta1-agonist (dobutamine) was used. No lipolysis-attenuating effect of PMA was found when cells were exposed to a beta2-agonist (procaterol) and beta3-agonists (BRL 37344 and CL 316243), or to forskolin and 8-bromo cAMP. CGP 20712A (beta1-antagonist) efficiently inhibited lipolysis by norepinephrine, isoproterenol, and dobutamine, but did not affect lipolysis by the beta2- and beta3-agonists. ICI 118551 (beta2-antagonist) had no significant effect on lipolysis by the beta-agonists examined. CGP 20712A abolished the lipolysis-attenuating effect of PMA, but ICI 118551 did not. The protein kinase C (PKC) inhibitors, GF 109203X or Gö 6976, suppressed the effect of PMA. Pretreatment of adipocytes with PMA for 6 h caused downregulation of conventional and novel PKCs in association with a decrease in the lipolysis-attenuating effect of PMA. These results indicate that conventional and novel PKCs attenuate lipolysis mediated by beta-adrenergic receptors, probably through inhibition of the beta1-adrenergic receptor system.
Nakamura
Jiro
J
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305-8575, Japan. jnakamur@sakura.cc.tsukuba.ac.jp
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D054769:G-Protein-Coupled Receptor Kinase 2; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*; D051552:beta-Adrenergic Receptor Kinases / Q000378:metabolism*
D011493:Protein Kinase C; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D013755:Tetradecanoylphorbol Acetate