INHIBITION OF CELLULAR GROWTH AND NUTRIENT TRANSPORT INDUCED BY CALCIUM IONOPHORE A23187 IN MASTOCYTOMA P-815 CELLS

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Kinetic analysis of Ca²⁺ metabolism in mastocytoma P-815 cells showed that at non-cytotoxic and growth-inhibitory concentrations (<10μg/ml), the calcium ionophore A23187 did not affect the rate constant (36.2 min^-1) or the compartment size (8.32 nmol/10⁶ cells) of the fast phase of calcium exchange at the cell surface. In contrast, A23187 (1 to 10μg/ml) dose-dependently increased the compartment size of slow phase I of the intracellular calcium uptake from 0.54 to 2.39 nmol/10⁶ cells without affecting the rate constant (2.38 min^-1). In addition, A23187 (5 to 10, μg/ml) produced an additional compartment [slow phase II] with a rate constant of 0.25 min^-1 and increased its compartment size from 0.42 to 1.26 nmol/10⁶ cells. A23187 (10μg/ml) in the presence of Ca²⁺ (0.9 mM) non-competitively inhibited the membrane transport of amino acids, glucose and nucleosides; and it also reduced the cellular ATP level and the membrane fluidity. Apparently, A23187 inhibits the growth of mastocytoma cells by elevating the intracellular concentration of Ca²⁺, which in turn reduces the membrane fluidity and the carrier-dependent as well as the active membrane transport of various nutrients required for cellular growth.