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 micromol. 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.