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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:44-51.)
© 1995 American Heart Association, Inc.

Articles

Platelet-Derived Growth Factor Causes Sustained Depletion of Both Inositol Trisphosphate-Sensitive and Caffeine-Sensitive Intracellular Calcium Stores in Vascular Smooth Muscle Cells

Smadar A. Lapidot; Robert D. Phair

From the Department of Biomedical Engineering (S.A.L., R.D.P.) and the Department of Physiology (R.D.P.), The Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Dr Robert D. Phair, Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205.

Abstract Since the platelet-derived growth factor (PDGF)–induced increase in cellular inositol 1,4,5-trisphosphate (InsP₃) has been found to decay to basal levels soon after the onset of PDGF exposure, it has been argued that activation of Ca²⁺ release from intracellular stores must be similarly transient. The possibility remains, however, that PDGF-induced release of stored Ca²⁺ is initiated and sustained by other second-messenger systems. To test the hypothesis that PDGF-BB initiates sustained Ca²⁺ release from cellular stores, we performed 4-hour ⁴⁵Ca effluxes on monolayers of A7r5 vascular smooth muscle cells in small, continuously perfused chambers. Isoform PDGF-BB (5 ng/mL for 30 minutes or 30 ng/mL for 15 minutes) was added to the perfusate beginning at 30 minutes of efflux. A dose-related increase in ⁴⁵Ca release was sustained as long as PDGF-BB was present. Detailed kinetic analysis and nonlinear least-squares fitting of the experimental data revealed that (1) PDGF-BB induced sustained increases of 2.86-fold (5 ng/mL) and 6.50-fold (30 ng/mL) in the rate constant governing Ca²⁺ release from intracellular stores, (2) the apparent K_m for this effect was 13.4±1.31 ng PDGF-BB/mL, and (3) the entire agonist-releasable Ca²⁺ store (presumably sarcoplasmic reticulum) is sensitive to PDGF-BB. These data indicate that PDGF-BB causes a sustained depletion of intracellular Ca²⁺ stores by means of sustained activation of Ca²⁺ release and suggest that intraorganellar Ca²⁺ may be one of the signals that mediates long-term smooth muscle responses to PDGF.

Key Words: calcium • ⁴⁵Ca • A7r5 cells • PDGF • tracer kinetics • vascular smooth muscle cells • SAAM

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