Electrogenic Na1 transport in rat late distal colon by natural and synthetic glucocorticosteroids

Grotjohann, Ingo, Jörg-Dieter Schulzke, and Michael Fromm. Electrogenic Na1 transport in rat late distal colon by natural and synthetic glucocorticosteroids. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G491–G498, 1999.—The potency of in vitro-added corticosteroids to stimulate electrogenic Na1 absorption (JNa, the Na1 absorptive short-circuit current blockable by 1024 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 1024 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 5 deoxycorticosterone 20 nM . deoxycortisol 36 nM $ dexamethasone 37 nM : corticosterone 170 nM . cortisol 210 nM. These steroids exhibited Vmax values of 9–13 μmol ·h21 ·cm22 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.