Acute effects of dexamethasone on cation transport in colonic epithelium.
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 micrograms/100 g body weight. Compared with control tissues, dexamethasone increased transepithelial voltage 3.5-fold (p less than 0.001) and short circuit current 4.5-fold (p less than 0.001), and decreased total resistance by 20% (p less than 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 less than 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/l amiloride (a Na+ channel blocker) and then 30 mmol/l 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.
D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium