Platelet-derived growth factor stimulates Na+ influx in vascular smooth muscle cells.
Platelet-derived growth factor (PDGF) is known to be a potent mitogenic agent for vascular smooth muscle cells. The effect of PDGF on amiloride-sensitive Na+ influx was investigated in A-10 vascular smooth muscle cells. At a dose which maximally stimulates DNA synthesis, PDGF stimulates net Na+ influx in vascular smooth muscle cells. The PDGF-stimulated Na+ influx is linear over a 5-min time course. PDGF stimulates Na+ influx in a concentration-dependent manner, with a concentration of 0.5 U/ml causing half-maximal inhibition. The effects of PDGF on Na+ influx can be mimicked by 10% fetal bovine serum or by the divalent cation ionophore A23187 (5 microM). Net Na+ influx in response to each of these agents was inhibited by amiloride and by benzamil. PDGF-stimulated net Na+ influx was blocked by the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate as well as by the calmodulin antagonists trifluoperazine, chlorpromazine, and imipramine. These data suggest that PDGF may stimulate an amiloride-sensitive Na+ influx pathway via an elevation in intracellular Ca2+ and formation of a Ca-calmodulin complex. This Na+ influx pathway may be a trigger for PDGF-stimulated DNA synthesis.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors
D002147:Calmodulin; D007473:Ion Channels; D010982:Platelet-Derived Growth Factor; D000584:Amiloride; D004247:DNA; D012964:Sodium; D002118:Calcium