Colonocyte basolateral membranes contain Escherichia coli heat-stable enterotoxin receptors

Heat-stable enterotoxin (STa) elaborated by E. coli is a major cause of dia rrhea. The transmembrane protein guanylyl cyclase C (GC-C) is the acknowled ged receptor for ST, and for the mammalian peptides guanylin and uroguanyli n. Binding to GC-C results in generation of cGMP, activation of type II cGM P-dependent protein kinase, phosphorylation of CFTR and increased chloride and bicarbonate secretion. We lead previously shown that STa receptors (GC- C) are found on the brush border membranes of small intestinal enterocytes and of colonocytes. However, since it has subsequently been shown that the endogenous ligands for these receptors; guanylin and uroguanylin, circulate in blood, we proposed the existence of ST, binding sites on the basolatera l membranes (BLM.) of colonocytes. Specific binding of I-125-STa to rat col onocyte BLM was seen. The kinetics of binding to the BLM were similar to bi nding to BBM. The nature of the BLM receptor is unknown. This suggests that circulating guanylin and uroguanylin, analogues of STa, may also function via the basolateral surface, (C) 2001 Academic Press.