Effect ofE. coliheat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3−Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+absorption, lower net Cl−absorption, and a negative residual ion flux ( JR), indicating net HCO3−absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl−( Js→mCl) and decreased net Cl−flux ( JnetCl) accompanied by increases in short-circuit current ( Isc), potential difference (PD), and tissue conductance ( G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon Js→mCland JnetCl, Isc, PD, G, and JRsimilar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.