Acute effects of dexamethasone on cation transport in colonic epithelium

Abstract

Single pharmacological doses of glucocorticoid hormones stimulate net Na+ and water absorption, K+ secretion and electrical potential difference in rat distal colon and human rectum after five hours. To determine the cellular basis of these effects, the Na+ and K+ transport properties of epithelial cell membranes in rat distal colon were studied in vitro five hours after in vivo treatment with dexamethasone 600 μ/100 g body weight. Compared with control tissues, dexamethasone increased transepithelial voltage 3·5-fold (p<0·001) and short circuit current 4·5-fold (p<0·001), and decreased total resistance by 20% (p<0·005). Measurements of cell membrane voltages obtained with intracellular microelectrodes indicated that the dexamethasone-induced rise in transepithelial voltage reflected a significant decrease (p<0·05) in apical membrane voltage, consistent with the induction of apical Na+ channels and the stimulation of electrogenic Na+ absorption. Apical addition of 10-4 mol/1 amiloride (a Na+ channel blocker) and then 30 mmol/1 tetraethylammonium chloride (TEA; a K+ channel blocker) to control tissues had little or no effect on transepithelial electrical parameters, indicating the absence of significant apical Na+ and K+ conductances. In contrast, in dexamethasone treated tissues, amiloride and TEA produced electrical changes that were consistent with the inhibition of glucocorticoid-induced apical Na+ and K+ conductances. Kinetic studies of the basolateral membrane Na+-K+ pump revealed that five hours after administration, dexamethasone had no effect on the maximum capacity of the pump for Na+ transport, but significantly increased the affinity of the pump for Na+, and the number of Na+ ions binding to each pump site. Thus, the acute stimulatory effects of dexamethasone on distal colonic Na+ absorption and K+ secretion reflect increased apical membrane conductance to Na+ and K+, and an increase in the 'efficiency' of the basolateral membrane Na+-K+ pump.