Assessment of mineralocorticoid activity in the rabbit colon

Analyses of [3H]corticosteroid binding sites in distal colon indicated high-affinity binding sites or receptors for both [3H]aldosterone (Type I, Kd = 6.5 X 10(-9) M) and [3H]dexamethasone (Type II, Kd = 5.5 X 10(-8) M). The relative affinity of dexamethasone (D) was 1/20 that of aldosterone (A) for Type I sites and the affinity of A for Type II sites was 1/50 that of D at 37 degrees C. Citrate synthase (CS) activity was assayed and found to be reduced in enterocytes harvested from adrenalectomized (ADX) vs. normal colon segments (0.24 vs. 0.44 U/mg protein, P less than 0.025). Aldosterone (10 micrograms/kg body wt) increased CS at 2 h to a level intermediate between normal and ADX animals and thus not significantly different from either group, but was significantly increased over ADX + D values. Transmural potential difference was increased by 10(-8) M A but not by 10(-8) M D. Since both steroids enhanced short-circuit current at this concentration, the dichotomy of the glucocorticoid vs. mineralocorticoid results can be best explained by the pronounced effect of D on resistance (R) across the tissue (R at 4 h + D was 50% that of paired controls). These findings would suggest that the rabbit distal colon is a target segment for both mineralocorticoids and glucocorticoids. Furthermore, as in the kidney, the two steroids may play coordinated but, perhaps in some way, unique roles in the regulation of transport.