Enhancement of adenosine A2 and prostaglandin E1 receptor-mediated cAMP generation by prior exposure of Swiss 3T3 fibroblasts to Ca2+-mobilizing receptor agonists or phorbol ester. Activation of protein kinase C triggers increases in the receptor density in cell membranes.
Production of cAMP in response to adenosine A2 or prostaglandin E1 receptor stimulation was, but the production induced by a beta-adrenergic agonist or forskolin was not, enhanced by prior exposure of Swiss 3T3 fibroblasts to agonists of Ca2+-mobilizing receptors or phorbol ester for 3 h. The enhancement reflected potentiation of the receptor-coupled activation of adenylate cyclase and the 2-fold increase in the adenosine A2 receptor number in membranes under these conditions. No enhancement was observed, however, when the medium used for the prior exposure was further supplemented with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) or staurosporin, inhibitors of protein kinase C, neither of which affected the cAMP responses of the nonexposed cells. It is very likely, therefore, that activation of protein kinase C triggers the increase in certain receptor density in membranes, thereby enhancing the receptor-coupled cAMP-generating responses. The physiological significance of such cross-talk between cellular signaling systems is discussed in comparison with similar previous observations.
Murayama
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Nomura
Y
Y
Ui
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D011983:Receptors, Purinergic; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D019311:Staurosporine; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium