Localization of Na,K-ATPase activity in developing rat distal colon: role of corticosteroids

The role of corticosteroids in the development of Na,K-ATPase and its distribution along the crypt base-colonic surface was investigated in suckling, weanling and adult rats using a biochemical and a histochemical approach. The cerium-based histochemical method for detection of ouabain-sensitive K+-dependent p-nitrophenylphosphatase (K-NPPase) component of the Na,K-ATPase complex was used to localize Na,K-ATPase in the epithelium. The activity of Na,K-ATPase was very low 2 days after birth and increased to a maximum in adulthood. Mature surface colonocytes and immature cells at the crypt base were similarly reactive and the reaction product was decreased by the addition of ouabain and inhibited by omission of K+. Adrenalectomy decreased colonic Na,K-ATPase activity in surface and deep crypt cells of suckling, weanling and adult animals. Mineralocorticoids (deoxycorticosterone acetate, DOCA) restored the Na,K-ATPase activity both in surface and crypt cells of adrenalectomized weanling rats and the effect of DOCA was inhibited by the mineralocorticoid receptor antagonist, spironolactone. Physiological doses of glucocorticoids (dexamethasone) stimulated Na,K-ATPase activity in surface colonocytes of adrenalectomized weanling rats; supraphysiological doses restored Na,K-ATPase probably via cross-over into mineralocorticoid receptors both in surface and crypt cells. High dietary Na+ intake during the weaning period reduced the reaction product to the level detected in adrenalectomized rats. The distribution of Na, K-ATPase activity in the epithelium of adrenalectomized rats with substitutional replacement hormone therapy was the same as in control animals or, in some animals, the surface absorptive epithelium exhibited a stronger reaction than the crypt cells. Similarly, the surface colonocytes of adult rats kept on a low-salt diet showed a stronger reaction than the crypt cells. These data indicate that postnatal development of Na,K-ATPase is regulated predominantly by aldosterone and that both surface and crypt cells are responsive to mineralocorticoids. Surface cells are also responsive to glucocorticoids.