Effect of spironolactone on glucocorticoid-induced colonic cation transport

Glucocorticoids stimulate colonic sodium absorption. Whether this stimulation is mediated by crossover binding to the aldosterone receptor has not been established. The effect of the aldosterone receptor antagonist, spironolactone, on dexamethasone-mediated transport was investigated in proximal and distal colon of adrenalectomized rats. In adrenal-intact control rats spironolactone minimally affected sodium absorption but markedly decreased the transmural potential difference (PD). In adrenalectomized, aldosterone-replaced rats spironolactone clearly decreased sodium absorption and transmural PD in both proximal and distal colon. In adrenalectomized rats treated with 5 micrograms/100 g body wt of dexamethasone twice daily spironolactone did not decrease sodium absorption or transmural PD. However, when adrenalectomized rats were treated with 25 micrograms/100 g body wt of dexamethasone, a dose estimated from plasma levels to occupy 80% of colonic aldosterone receptors, spironolactone inhibited 20% of proximal colon and 47% of distal colon sodium absorption. Thus lower doses of glucocorticoid which predominantly occupy glucocorticoid receptors stimulate sodium absorption by a spironolactone independent mechanism. When the levels of glucocorticoid are high enough to also occupy the majority of aldosterone receptors, sodium absorption is stimulated by an aldosterone receptor mediated mechanism.