Secretin receptors mediating rat forestomach relaxation

Frozen sections of the rat stomach were incubated with 125I-labeled porcine secretin, and then secretin binding sites were localized by autoradiography. Saturable binding was observed only in the muscularis externa (circular and longitudinal smooth muscle layers) of the proximal nonglandular forestomach. Saturable binding was quantitated by densitometry. 125I-porcine secretin bound to a single class of high-affinity binding sites with a dissociation constant of 0.6 nM. Porcine and rat secretins were nearly equipotent in inhibiting saturable 125I-porcine secretin binding, and vasoactive intestinal polypeptide, peptide histidine-isoleucine, and glucagon were much weaker. Carbachol (100 microM) stimulated a sustained increase in tension in forestomach muscle in vitro, and porcine secretin caused relaxation of this stimulated contraction. We conclude that rat forestomach smooth muscle expresses a high-affinity specific secretin binding site that mediates relaxation. This putative secretin receptor may mediate some of the actions of secretin on gastric motility.