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

Abstract

The potency of in vitro-added corticosteroids to stimulate electrogenic Na+absorption ( J Na, the Na+ absorptive short-circuit current blockable by 10−4 M amiloride) was determined in rat late distal colon. J Na was determined 8 h after steroid addition from the drop in short-circuit current caused by 10−4 M amiloride. The concentration dependency of J Na was obtained for seven corticosteroids and compared with that established for aldosterone. Apparent mineralocorticoid potencies as determined from apparent Michaelis-Menten constant ( K m) 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 V max values of 9–13 μmol ⋅ h−1 ⋅ cm−2and 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 K m value of RU-28362 for mineralocorticoid action and the need for high concentrations of the mineralocorticoid antagonist mespirenone to block this response indicated that J Na 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 J Na by the glucocorticoid receptor and mineralocorticoid receptor.