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Inhibition of rabbit aortic smooth muscle cell proliferation by selective inhibitors of protein kinase C
Author(s) -
Newby Andrew C.,
Lim Karene,
Evans Marilyn A.,
Brindle Nicholas P.J.,
Booth Robert F.G.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14953.x
Subject(s) - platelet derived growth factor receptor , protein kinase c , activator (genetics) , platelet derived growth factor , tyrosine kinase , protein kinase a , cell growth , biology , endocrinology , medicine , growth factor , kinase , chemistry , microbiology and biotechnology , biochemistry , receptor
1 We studied the effect of two structurally‐related, selective inhibitors of protein kinase C, Ro 31–8220 and Ro 31–7549, on the reinitiation of proliferation in quiescent first passage rabbit aortic smooth muscle cells in response to (a) the direct activator of protein kinase C, phorbol dibutyrate (PDBu), (b) platelet‐derived growth factor (PDGF), (c) a combination of PDGF and 5‐hydroxytryptamine (5‐HT) or (d) serum. 2 Ro 31–8220 and Ro 31–7549 concentration‐dependently inhibited prliferation in response to each mitogen. The inhibitory potency (IC 50 ) of Ro 31–8220 and Ro 31–7549, respectively, was similar against proliferation induced by PDBu (0.55 and 1.1 μm), PDGF (0.6 and 0.9 μm), PDGF and 5‐HT (0.68 and 1.1 μm), although slightly less against serum (1.7 and 5 μm). The effects of the protein kinase C inhibitors on proliferation could not be ascribed to cytotoxicity. Neither Ro 31–8220 nor Ro 31–7549 (0.3‐3 μm) inhibited PDGF receptor tyrosine phosphorylation. 3 The results show that Ro 31–8220 and Ro 31–7549 are potent inhibitors of smooth muscle cell proliferation in response to a direct activator of protein kinase C, the defined growth factors, PDGF and 5‐HT, and the complex mixture of mitogens in serum. Protein kinase C activation thus appears to be an important growth transducing mechanism for each of these agents.