Unanticipated stimulatory action of glucocorticoids on epithelial calcium absorption. Effect of dexamethasone on rat distal colon.

UNLABELLED

We studied the action of a glucocorticoid (GC, dexamethasone) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on transepithelial calcium (Ca) transport in rat distal colon. GC 1.2 mg or 1,25(OH)2D3 270 ng were given daily for 4 d and Ca fluxes were measured in vitro in the absence of electrochemical gradients (Ussing technique).

RESULTS

(a) Both 1,25(OH)2D3 and GC increased Ca absorptive flux from 24 +/- 3 (SEM) to 50 +/- 1 and from 23 +/- 1 to 38 +/- 4 nmol/cm2 per h, respectively (in each case n = 9, P less than 0.01); both steroid hormones had no effect on Ca secretory flux. (b) GC, but not 1,25(OH)2D3 increased the short-circuit current Isc) from 30 +/- 5; to 111 +/- 13 microA/cm2 (P less than 0.01), reflecting stimulation of electrogenic sodium (Na) transport. Choline replacement of Na in the bathing buffer abolished both the Isc and the active Ca transport induced by GC, but has no effect on the 1,25(OH)2D3-stimulated active Ca absorption. (c) When the buffer Ca concentration ([Ca]) on both sides of the epithelium was reduced from 1.25 to 1.25 X 10(-2) mM, the GC-induced, but not the 1,25(OH)2D3-induced, stimulation in Ca absorption was abolished. This suggests that the GC-stimulated Ca absorption may require a "threshold" Ca gradient across the luminal membrane through which Ca influx occurs. Thus, contrary to the current consensus, this study demonstrates that GC stimulates active Ca transport and that this action is mediated through a mechanism dependent on the presence of Na and a critical [Ca] in the ambient medium.