Platelet-derived growth factor (PDGF)-induced phospholipase C-mediated hydrolysis of phosphoinositides in vascular smooth muscle cells--different sensitivity of PDGF- and angiotensin II-induced phospholipase C reactions to protein kinase C-activating phorbol esters.
In cultured rabbit vascular smooth muscle cells (VSMC), platelet-derived growth factor (PDGF), a potent mitogen for VSMC, induced the dose- and time-dependent formation of inositol mono-, bis- and trisphosphates (IP1, IP2 and IP3, respectively). The doses of PDGF necessary for these reactions were similar to those for DNA synthesis. The maximal level of IP1 was comparable to, and those of IP2 and IP3 were about half of those induced by angiotensin II, a potent vasoconstrictor. However, the time courses of the PDGF-induced reactions were slower than those of the angiotensin II-induced ones. Moreover, protein kinase C-activating phorbol esters inhibited the angiotensin II-induced reactions, but did not the PDGF-induced ones. These results indicate that PDGF induces the phospholipase C reactions in VSMC but suggest that the signaling mechanism of PDGF to the phospholipase C is different from that of angiotensin II.
Kawahara
Y
Y
Department of Internal Medicine (1st Division), Kobe University School of Medicine, Japan.
Kariya
K
K
Araki
S
S
Fukuzaki
H
H
Takai
Y
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D004247:DNA; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate