Complex actions of protein kinase A inhibitors on mitogenesis of bovine coronary artery smooth muscle cells.
This study investigates the possible modulation of platelet-derived growth factor-(PDGF, 20 ng/ml)-induced DNA synthesis in bovine coronary artery smooth muscle cells by the protein kinase A inhibitors Rp-adenosine-3',5'-cyclic phosphorothioate (Rp-cAMPS, 0. 03-10 microM) and ¿N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, HCl¿ (H-89, 0.01-1 microM). Rp-cAMPS concentration dependently enhanced PDGF-induced DNA synthesis. In contrast, no potentiation of PDGF-induced DNA synthesis was seen with H-89. However, H-89 but not Rp-cAMPS, inhibited p42/p44 mitogen-activated protein kinase phosphorylation. Thus, Rp-cAMPS, but not H-89, unmasks inhibitory actions of protein kinase A on PDGF-induced mitogenesis of vascular smooth muscle cells. Low specificity may limit the use of H-89 as protein kinase A inhibitor.
Osinski
M T
MT
Institut für Pharmakologie und Klinische Pharmakologie, Moorenstrasse 5, D-40225, Düsseldorf, Germany.
Weber
A
A
Schrör
K
K
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D013449:Sulfonamides; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D004247:DNA; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide