Protein kinase C potentiates isoproterenol-mediated cyclic AMP production without modifying the homologous desensitization process in J774 cells.
The J774 murine macrophage cells possess a beta 2-adrenergic receptor coupled to adenylate cyclase, which can be regulated by homologous desensitization. Stimulation of protein kinase C by phorbol esters or oleoyl acetyl glycerol potentiates two-to-threefold the isoproterenol-induced cyclic AMP accumulation. These promoters act at a post-receptor level, since the number and affinity of the beta-adrenergic receptors, measured by use of the hydrophilic ligand [3H]CGP-12177, are not modified. In addition, the effect of cholera toxin is similarly increased and pretreatment of the cells with pertussis toxin prevents the action of phorbol esters. On the other hand, these promoters are ineffective on isoproterenol-induced desensitization and the rates of receptor segregation and recovery remain unchanged. Therefore, protein kinase C modulates the isoproterenol-stimulated adenylate cyclase, whereas it is inactive on the homologous desensitization process.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D010703:Phorbol Esters; D011943:Receptors, Adrenergic, beta; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine