Characterization of cholecystokinin A and cholecystokinin B receptors expressed by vagal afferent neurons

Abstract

The cholecystokinin receptors expressed by vagal afferent neurons mediate the effect of cholecystokinin in inhibiting food intake and gastric emptying. We have determined the relative abundance of cholecystokinin A, gastrin-cholecystokinin B and gastrin-cholecystokinin C receptor populations in the rat vagus by autoradiography using [ 125I]Bolton Hunter-cholecystokinin-8, [ 125I]Bolton Hunter-heptadecapeptide gastrin and [ 125I]Leu 152-17Glycine-extended heptadecapeptide gastrin, together with the selective antagonists devazepide and l-740 093. The results indicate approximately three-fold higher abundance of cholecystokinin A compared with gastrin-cholecystokinin B receptors, and no significant representation of gastrin-cholecystokinin C receptors. Topical capsaicin applied to the vagal nerve trunk abolished the accumulation of sites binding both [ 125I]Bolton Hunter-labelled cholecystokinin-8 and heptadecapeptide gastrin indicating that both cholecystokinin A and gastrin-cholecystokinin B receptor populations were present on afferent fibres. The molecular identity of the receptors expressed by rat and human nodose ganglia was examined using the reverse transcription polymerase chain reaction. Products of the predicted size for the cholecystokinin A and gastrin-cholecystokinin B receptors were identified. The human and rat cholecystokinin A receptor products were cloned and the sequences were found to be 99% homologous to those published for receptors expressed by rat pancreas and human gall bladder. We conclude that cholecystokinin A and gastrin-cholecystokinin B receptors are synthesized by nodose ganglion cells, and that the receptor proteins are transported to the periphery along afferent fibres. While there is a clear role for vagal cholecystokinin A receptors, the function of vagal afferent gastrin-cholecystokinin B receptors remains to be determined.