MODULATION OF CALCIUM-UPTAKE IN CULTURED CARDIAC-MUSCLE-CELLS BY 1,25-DIHYDROXYVITAMIN D-3

Recent studies have provided evidence indicating that 1,25-Dihydroxyvi taamn D-3 [1,25(OH)(2)D-3] rapidly stimulates calcium influx through C a2+ channels in isolated chick heart tissue and cells. Studies were pe rformed both to evaluate the characteristics of the hormone action in cultured myocytes and to obtain information on the metabolic pathway w hich mediates its effects. Treatment of 70-80% confluent chick embryo myocyte monolayers with 1,25(OH)(2)D-3 induced a fast (within 3-5 min) stimulation of Ca-45 uptake which was dose-dependent, maximum respons es (130% above controls) being elicited at a concentration of 10(-10)M . Physiological levels of 25(OH)D-3 and 24,25(OH)(2)D-3, and the synth etic analog 1 alpha(OH)D-3, had lower activity. Coincident with the ra pid changes in Ca uptake, 1,2 5(OH)(2)D-3, significantly increased cAM P levels. The hormone-induced increase in cAMP was not blocked by nife dipine. Compound SQ 22536, a specific inhibitor of adenylate cyclase, completely suppressed the effects of the sterol on cAMP and Ca uptake. Furthermore, GDP-beta-S inhibited the increase in Ca uptake by 1,25(O H)(2)D-3. These results involve the adenylate cyclase pathway and the participation of G proteins in 1,2 5(OH)(2)D-3 stimulation of Ca influ x in chick heart cells.