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

The potency of in vitro-added corticosteroids to stimulate electrogenic Na absorption (J(Na), the Naf absorptive short-circuit current blockable by 1 0(-4) M amiloride) was determined in rat late distal colon. J(Na) was deter mined 8 h after steroid addition from the drop in short-circuit current cau sed by 10-4 NI amiloride. The concentration dependency of JNa was' obtained for seven corticosteroids and compared with that established for aldostero ne. Apparent mineralocorticoid potencies as determined from apparent Michae lis-Menten constant (K-m) values were as follows: aldosterone 1.2 nM much g reater than RU-28362 20 nM = deoxycorticosterone 20 nM > deoxycortisol 36 n M greater than or equal to dexamethasone 37 nM much greater than corticoste rone 170 nM > cortisol 210 nM. These steroids exhibited V-max values of 9-1 3 mu mol . h(-1) . cm(-2) and similar concentration dependencies. Hill coef ficients were between 1.6 and 2.1, suggesting cooperative effects between a ctivated receptors. We conclude that corticosteroids exhibit graded mineral ocorticoid potency instead of a sharp partition into exclusive groups of mi neralocorticoid and nonmineralocorticoid hormones. The low apparent K-m val ue of RU-28362 for mineralocorticoid action and the need for high concentra tions of the mineralocorticoid antagonist mespirenone to block this respons e 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 a ldosterone or of the mineralocorticoid antagonist spironolactone showed coo perative action, suggesting a heterodimeric activation of J(Na) by the gluc ocorticold receptor and mineralocorticoid receptor.