The calcium antagonist nisoldipine and the calmodulin antagonist W‐7 synergistically inhibit initiation of DNA synthesis in cultured arterial smooth muscle cells
- 1 January 1987
- journal article
- research article
- Published by Wiley in Biology of the Cell
- Vol. 60 (2), 125-132
- https://doi.org/10.1111/j.1768-322x.1987.tb00552.x
Abstract
Cultured arterial smooth muscle cells go through a transition from a contractile to a synthetic phenotype. Morphologically, the transition includes a reduction in size of the myofilament bundles and the formation of an extensive rough endoplasmic reticulum and a large Golgi complex. Functionally, it leads to loss of contractility, onset of cellular proliferation, and secretion of extracellular matrix components. This change in differentiated characteristics under in vitro conditions has attracted attention because of its resemblance to the modification of the smooth muscle cells that occurs in vivo during atherogenesis. Here, transmission electron microscopy and [3H]‐thymidine autoradiography were used to study the role of calcium ions in the control of phenotypic properties and growth of cultivated rat aortic smooth muscle cells. The calcium antagonist nisoldipine was found to lack distinct effect on the structural reorganization of the cells, but showed a moderate prohibitory effect on the start of DNA synthesis early in primary culture. In growth‐arrested secondary cultures, nisoldipine inhibited induction of DNA synthesis by serum or platelet‐derived growth factor (PDGF). The agent's effect was inversely related to the concentration of calcium ions in the extracellular medium and was partially counteracted by the calcium agonist BAY K 8644. In contrast, W‐7, an antagonist of the calcium‐binding protein calmodulin, potentiated the effect of nisoldipine and, at higher concentrations, inhibited induction of DNA synthesis in itself. The results suggest that the mitogenic stimulation of arterial smooth muscle cells involves a flux of calcium ions through the plasma membrane and requires participation of calmodulin.This publication has 17 references indexed in Scilit:
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