Methylprednisolone stimulation of guanylate cyclase activity in rat small intestinal mucosa: Possible role in electrolyte transport

Abstract

A single, intramuscular dose of the glucocorticoid methylprednisolone (3 mg/100 g) significantly increased rat jejunal and ileal mucosal guanylate cyclase (GTP pyrophosphatelyase [cyclizing]; EC 4.6.1.2) activity and cyclic GMP concentration 6 h after treatment. This increase in guanylate cyclase activity was maximal 6 h after injection, was not associated with changes in mucosal cyclic AMP concentration, and occurred before any increase in NaK-activated adenosine triphosphatase activity could be detected. In contrast to the findings in the small intestine, no alterations in guanylate cyclase activity were present in the rat colon 6 or 72 h after methylprednisolone treatment. The increase in ileal guanylate cyclase activity and cGMP concentration coincided with increases in ileal short-circuit current, potential difference, net Cl secretion, and serosal-to-mucosal unidirectional Cl flux. In contrast, in the colon, where no changes in guanylate cyclase activity were observed, methylprednisolone did not alter electrolyte transport in vitro. A similar correlation was observed between various methylprednisolone doses, the increase in guanylate cyclase activity and the alteration in ileal short-circuit current and net Cl transport. The methylprednisoloneinduced increase in ileal guanylate cyclase activity was not prevented by pretreatment with the mineralocorticoid competitive inhibitor spironolactone, nor did the mineralocorticoid deoxycorticosterone acetate (0.5 mg/100 g) affect ileal or colonic mucosal guanylate cyclase activity. In addition, isolated enterocytes from methylprednisolone-treated animals exhibited significant increases in guanylate cyclase activity with the greatest percentage increase occurring in the crypt cell population. These results suggest that the changes in chloride transport which occurred in the small intestine 6 h after methylprednisolone administration may be due to alterations in guanylate cyclase activity, and further support the role of cGMP as an intracellular mediator of ileal chloride secretion.