The Effect of Platelet-Derived Growth Factor on Tone and [Ca2+]i in Vascular Smooth Muscle
Platelet derived growth factor (PDGF) is a cationic protein first described in platelets (8). PDGF is now known to be produced by a variety of cell types including endothelial cells, vascular smooth muscle cells and macrophages/monocytes (reviewed in 4). PDGF exists in multiple molecular weight isoforms which are composed of two chains (A & B) which share considerable homology. All possible dimeric forms of PDGF have been described (PGDF-AA, PDGF-BB, PDGF-AB), although the dominant isoform produced varies depending on cell type and experimental conditions (4). PDGF is a potent mitogen for vascular smooth muscle cells (4, 13) and may account for 50% of the mitogenic action of platelets (6). PDGF also contracts vascular smooth muscle in some (2, 3), but not all sites (1). PDGF-induced vasoconstriction is reported to be unaffected by antagonists of α-adrenoceptors, 5HT2 receptors or cyclo-oxygenase (3) and presumably involves a direct action on the PDGF receptor, although the mechanism of this effect is unclear. PDGF interacts with a membrane associated receptor to induce receptor dimerization and autophosphorylation on multiple tyrosine sites (10). These phosphotyrosine residues can then interact with a variety of intracellular mediators by a process involving binding to SH2 domains in the effector proteins. Phospholipase C-γ, phosphatidyl-inositol-3 kinase, GTP-ase activating protien for p21 ras (GAP) and p21 ras all appear to be activated by PDGF in this way (10). The role of one or any of these systems in PDGF-induced contraction of vascular smooth muscle is unknown. Therefore this study examined the possible role of changes in intracellular Ca2+ (Cai) in the contractile action of PDGF in isolated rabbit ear artery using the fluorescent indicator fura-2 (14,15).
KeywordsVascular Smooth Muscle Cell Platelet Derive Growth Factor Platelet Derive Growth Factor Receptor Dihydropyridine Calcium Antagonist Calcium Channel Current
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