. Effects of Calcitriol, Calcipotriol and 20 epi- Vitmin D3 analogue MC 1288 on calcium influx, membrane protein phosphorylation and DNA synthesis in cultured muscle cells

SELLES JUANA; MASSHEIMER VIRGINIA; SANTILLAN GRACIELA; MARINISEN JULIA; BOLAND R

BIOCHEMICAL PHARMACOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 1997 vol. 53 p. 1807 - 1814

0006-2952

The fast actions of the secosteroid hormone 1á,25-dihydroxyvitamin D3 [1,25(OH)2D3; calcitriolJ and the synthetic analogues calcipotriol (MC 903) and 20-epi-1á,25(OH)2D3 (MC 1288) on cell calcium influx were compared in rat duodenum enterocytes as well as in cells from chick embryo skeletal muscle (myoblasts) and heart (myocytes), at various concentrations (10−12 to 10−8 M) and treatment intervals (1–10 min). In enterocytes, at a concentration of 10−11 M, MC 1288 was significantly more active than 1,25(OH)2D3 in rapidly stimulating 45Ca2+ uptake by enterocytes (80 vs 38% above controls, respectively), whereas MC 903 was devoid of activity. However, calcipotriol increased Ca2+ influx in myocytes and myoblasts to a greater extent than the natural hormone, whereas MC 1288 was more active only in myoblasts. Analogously to 1,25(OH)2D3, the fast MC 903- and MC 1288-induced stimulation of 45Ca2+ uptake in enterocytes and muscle cells could be blocked by both verapamil and nifedipine. In addition, MC 903 and MC 1288 were more effective than 1,25(OH)2D3 in stimulating DNA synthesis in proliferating myoblasts and in inhibiting DNA synthesis in differentiating myoblasts. The results suggest, therefore, that modifications in the side-chain of the 1,25(OH)2D3 molecule increase its ability to modulate muscle cell Ca2+ metabolism and growth. These findings are potentially relevant for the development of analogues for the treatment of vitamin D-dependent myopathies