Receptors for Escherichia coli heat stable enterotoxin in human intestine and in a human intestinal cell line (Caco-2)

Escherichia coli heat stable enterotoxin (ST_a) and the newly identified endogenous ligand guanylin bind to an intestinal receptor and activate membrane bound guanylate cyclase. We compared ST_a binding and affinity crosslinking of ST_a receptors in human small intestine to those in the Caco-2 human colon carcinoma cell line. ST_a had similar kinetics of binding in human intestinal and Caco-2 brush border membranes. In both human intestine and Caco-2 brush border membranes, multiple specifically radiolabeled bands, including a 140–165 kDa band, were identified by affinity crosslinking. However, in human intestine the most prominent autoradiographic species was a 60 kDa band. A 60 kDa protein was also specifically immunoprecipitated from solubilized human brush border membranes using antisera raised against a cloned ST_a receptor fusion protein. Our observations of multiple crosslinked proteins in human intestine and Caco-2 cells could be explained by the existence of several members of a family of ST_a receptors and/or the existence of smaller ST_a binding proteins generated by the protease cleavage of a larger complete ST_a receptor. © 1993 Wiley-Liss, Inc.