Platelet-Derived Growth Factor Activates Phospholipase D and Chemotactic Responses in Vascular Smooth Muscle Cells

• Published in: In Vitro Cellular & Developmental Biology - Animal Vol. 27A; no. 5; pp. 425 - 431
• Main Authors: Clement J. Welsh, Karen Schmeichel, McBride, Kevin
• Format: Journal Article
• Language: English
• Published: United States Tissue Culture Association, Inc 01-05-1991
• Subjects: Animals; Cell Division - drug effects; Cell growth; Cell Line; Chemotaxis; Chemotaxis - drug effects; Choline - metabolism; Cultured cells; Diglycerides; Diglycerides - metabolism; Dimers; Dose-Response Relationship, Drug; Enzyme Activation; Glycerophospholipids; Hydrolysis; Kinetics; Macromolecular Substances; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Phosphatidic acids; Phosphatidic Acids - metabolism; Phosphatidylcholines; Phospholipase D - drug effects; Phospholipids - metabolism; platelet-derived growth factor; Platelet-Derived Growth Factor - pharmacology; Rapid Communications in Cell Biology; Rats; Receptors; smooth muscle; Smooth muscle myocytes
• ISSN: 0883-8364; 2327-431X; 1543-706X
• DOI: 10.1007/BF02630963

Platelet-derived growth factor (BB dimer; PDGF-BB) stimulates a mitogenic response in A-10 vascular smooth muscle cells. In addition, PDGF-BB stimulates phospholipase D activity against phosphatidylcholine in A-10 cells. This response was observed as a rapid metabolism of phosphatidylcholine to phosphatidate and choline; a subsequent metabolism generates sustained levels of diacylglycerol. The accumulation of phosphatidylethanol, a transphosphatidylation product of phospholipase D, was obvious in PDGF-treated cells. PDGF-BB also stimulates a chemotactic response in A-10 cells. The concentrations of PDGF-BB required to stimulate mitogenesis, phospholipase D activity and chemotaxis are similar. This finding shows that PDGF induces a variety of cellular responses and suggests that these responses may share common metabolic pathways. That conception was tested by investigating the activity of the different PDGF dimers. PDGF-AA had little or no activity in A-10 cells for any of the responses measured. PDGF-AB and PDGF-BB were equally potent in stimulating mitogenic responses. However, the AB heterodimer was only half as active as PDGF-BB with respect to activation of phospholipase D and chemotactic responses. These results demonstrate that PDGF stimulates phospholipase D in vascular smooth muscle cells. In addition, the data indicate that different PDGF dimers can transduce varying signals and suggest a link between the mechanisms by which PDGF-BB activates phospholipase D and the chemotactic response.