Comparison of aldosterone- and RU-28362-induced apical Na+ and K+ conductances in rat distal colon.
In mammalian distal colon, aldosterone induces electrogenic Na+ absorption and electrogenic K+ 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 cells and crypt cells were devoid of apical Na+ and K+ conductances. In aldosterone-treated animals (70 micrograms.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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lomax
R B
RB
Department of Medicine, University of Manchester, Hope Hospital, Salford, United Kingdom.
Sandle
G I
GI
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D004553:Electric Conductivity; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000502:physiology*; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000732:Androstanols; D000838:Anions; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D000450:Aldosterone; D019789:Tetraethylammonium; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D012964:Sodium; D011188:Potassium