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Am J Physiol Gastrointest Liver Physiol 276: G491-G498, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 2, G491-G498, February 1999

Electrogenic Na+ transport in rat late distal colon by natural and synthetic glucocorticosteroids

Ingo Grotjohann1, Jörg-Dieter Schulzke2, and Michael Fromm1

1 Institut für Klinische Physiologie and 2 Medizinische Klinik I Gastroenterologie und Infektiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany

The potency of in vitro-added corticosteroids to stimulate electrogenic Na+ absorption (JNa, the Na+ absorptive short-circuit current blockable by 10-4 M amiloride) was determined in rat late distal colon. JNa was determined 8 h after steroid addition from the drop in short-circuit current caused by 10-4 M amiloride. The concentration dependency of JNa was obtained for seven corticosteroids and compared with that established for aldosterone. Apparent mineralocorticoid potencies as determined from apparent Michaelis-Menten constant (Km) values were as follows: aldosterone 1.2 nM >> RU-28362 20 nM = deoxycorticosterone 20 nM > deoxycortisol 36 nM >=  dexamethasone 37 nM >> corticosterone 170 nM > cortisol 210 nM. These steroids exhibited Vmax values of 9-13 µmol · h-1 · cm-2 and similar concentration dependencies. Hill coefficients were between 1.6 and 2.1, suggesting cooperative effects between activated receptors. We conclude that corticosteroids exhibit graded mineralocorticoid potency instead of a sharp partition into exclusive groups of mineralocorticoid and nonmineralocorticoid hormones. The low apparent Km value of RU-28362 for mineralocorticoid action and the need for high concentrations of the mineralocorticoid antagonist mespirenone to block this response indicated that JNa in a native mammalian epithelium can be mediated by the glucocorticoid receptor. Glucocorticoid receptor-specific amounts of RU-28362 in combination with mineralocorticoid receptor-specific amounts of aldosterone or of the mineralocorticoid antagonist spironolactone showed cooperative action, suggesting a heterodimeric activation of JNa by the glucocorticoid receptor and mineralocorticoid receptor.

short-circuit current; corticosterone; RU-28362; spironolactone; heterodimerization


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