COMPARISON OF ALDOSTERONE-INDUCED AND RU-28362-INDUCED APICAL NA+ AND K+ CONDUCTANCES IN RAT DISTAL COLON

In mammalian distal colon, aldosterone induces electrogenic Na+ absorption and electrogenic Kt secretion, whereas the sole transport effect of specific glucocorticoid agonists is thought to be stimulation of electroneutral NaCl absorption. In this study, intracellular microelectrodes and Na+- and K+-channel blockers were used to compare the effects of aldosterone and RU-28362 (a specific glucocorticoid agonist) on apical Na+ and K+ conductances in surface cells and upper crypt cells in the most distal colonic segment from adrenalectomized rats. In control animals, surface eels and crypt cells were devoid of apical Na+ and K+ conductances. In aldosterone-treated animals (70 mu g.100 g body wt(-1) day(-1) for 7 days), Na+ conductances were induced in 88% of surface cells but only 40% of crypt cells, and the distribution of K+ conductances was similar (82% of surface cells and 50% of crypt cells). The same dose of RU-28362 also induced Na+ conductances in 82% of surface cells and 50% of crypt cells, which tended to be smaller than those induced by aldosterone. RU-28362, in contrast to aldosterone, had no effect on apical K+ conductance in surface cells or crypt cells. Concurrent treatment with the mineralocorticoid antagonist RU-28318 (3.5 mg.100 g body wt(-1).day(-1) for 7 days) inhibited Na+-channel expression in aldosterone-treated animals but had no effect in RU-28362-treated animals. We conclude that in the most distal segment of rat colon, aldosterone acts via mineralocorticoid receptors to induce apical Na+ and K+ conductances, which are only fully expressed in the surface cell population. RU-28362 acts via glucocorticoid receptors to induce apical Na+ conductances in surface cells but, unlike aldosterone, has no effect on apical K+ conductance.