Effect of E-coli heat-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 pent obarbital sodium, and colon segments were studied in Ussing chambers in HCO 3- 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 sero sal-to-mucosal flux of Cl- (J(s-->m)(Cl) Cl) and decreased net Cl- flux (J( net)(Cl)) accompanied by increases in short-circuit current (Isc), potentia l difference (PD), and tissue conductance (G). Serosal STa had no effect. I n distal colon neither mucosal nor serosal STa affected ion transport. In r eceptor-deficient mice, neither mucosal nor serosal 500 nM STa affected ele ctrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo -cGMP produced changes in proximal colon J(s-->m)(Cl) and J(net)(Cl), I-sc, PD, G, and J(R) similar to mucosal STa addition in normal mice. We conclud e that the GCC receptor is necessary in the mouse proximal colon for a secr etory response to mucosal STa.