Summary
The effects of diltiazem, a calcium channel inhibitor, on the cellular transport of calcium were studied in isolated heterogenous rat bone cells. Efflux was measured after equilibrating the cells with 45 Ca and adding the vitamin D metabolite (1,25dihydroxycholecalciferol-1,25(OH)2 D3 or 24,25dihydrocholecalciferol-24,25(OH)2 D3 ), the ionophore A23187 and/or diltiazem. Results were analysed by fitting the desaturation curve to a model of two exponential terms. Kinetic analyses of curve indicated the presence of 2 exchangeable pools with different rate constants of exchange between the medium and cells (expressed by K.).
After incubation of bone cells with diltiazem (20 nmol/106 cells) the following changes were recorded: a marked decrease in the rate constant of efflux from the fast turnover calcium pool (K12 ) and a reduction of the calcium pool sizes. Incubation of 106 cells with 0.5 ng 1,25(OH)2 D3 plus diltiazem significantly reduced K12 compared to incubation with 1,25(OH)2 D3 alone. In presence of 24,25(OH)2 D3 , diltiazem did not significantly alter K12 which was raised by incubation with the metabolite alone. Ionophore A23187 (0.5 ug/106 cells) increased the value of slow turnover constants of efflux whose values were affected by diltiazem.
The possible involvement of Ca movements in bone resorption does not seem confirmed in the present experiment since in vitro effects of diltiazem in organ culture (observed in an initial previous experiment) were not reflected in the calcium 45 desaturation kinetics in heterogenous bone cells.
Key-Words
Bone Resorption
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45 Ca Efflux
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Calcium Antagonist
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Ionophore A23187
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Vitamin D Metabolites
