GUANYLYL CYCLASE RECEPTORS AND GUANYLIN-LIKE PEPTIDES IN REPTILIAN INTESTINE

Receptors for guanylin and uroguanylin were identified on the mucosal surface of enterocytes lining the intestine of the bobtail skink (Tili qua rugosa), king's skink (Egernia kingii), and knight anole (Anolis e questris) by receptor autoradiography using I-I25-ST (Escherichia coli heat-stable enterotoxin) as the radioligand. Specific, high-affinity binding of I-125-ST to receptors was found on the microvillus border o f enterocytes and little or no specific binding of I-125-ST was observ ed in other strata comprising the gut wall. The American alligator (Al ligator mississippensis) also exhibited receptor binding, but unlike t he other three species had relatively high levels of apparent nonspeci fic binding. A comparison of intestinal cGMP accumulation responses be tween the American alligator and the knight anole demonstrated a great er magnitude of cGMP responses to ST and guanylin in vitro in the knig ht anole relative to the tissue cGMP accumulation responses of alligat ors. Treatment with ST resulted in markedly greater tissue cGMP accumu lation responses in both species compared to treatment with guanylin. To complete a paracrine signaling pathway in reptilian intestine, guan ylin-like peptides that stimulated cGMP accumulation in human T-84 int estinal cells were isolated from the intestinal mucosa of alligators. We conclude that functional receptor-guanylyl cyclases and one or more endogenous guanylin/uroguanylin-like peptides of cur in the intestina l tract of reptiles as well as in the intestines of mammals and birds. Thus, higher vertebrates have a conserved signaling pathway that regu lates intestinal function through the first-messenger peptides, guanyl in and/or uroguanylin, and the intracellular second messenger, cGMP. ( C) 1997 Academic Press.