Effects of verapamil and dexamethasone on the 1,25-dihydroxyvitamin D 3-mediated calcium absorptive mechanism in the organ-cultured embryonic chick duodenum

Abstract

1,25-Dihydroxyvitamin D 3 (1,25(OH) 2D 3) is known to induce the biosynthesis of a specific, calcium-bincling protein (CaBP) and to stimulate calcium transport in the organ-cultured embryonic chick duodenum. The biosynthesis of CaBP has been shown previously to exhibit an absolute dependence on the ambient calcium concentration of the culture medium. Verapamil, a calcium-channel blocker, decreased calcium influx into the organ-cultured duodenum and inhibited the induction of CaBP by 1,25(OH) 2D 3. Raising ambient calcium concentrations to as high as 10 mM did not prevent or reverse the inhibitory actions of verapamil. Dexamethasone, known to augment CaBP biosynthesis and calcium uptake in the organ-cultured duodenum in response to 1,25(OH) 2D 3, largely prevented inhibition of CaBP by verapamil. The actions of verapamil and dexamethasone were correlated with altered steady-state calcium concentrations of the organ-culture duodenum, strongly supporting a regulatory role of calcium in the 1,25(OH) 2D 3-mediated, intestinal calcium absorptive mechanism.