Localization and characterization of neuropeptide receptors in human colon.
Information about the expression of neuropeptide receptors is limited in human peripheral tissues, such as the gastrointestinal tract, as compared to the brain. A detailed evaluation of binding sites for gastrin-releasing peptide (GRP), neuropeptide Y, vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin/cholecystokinin, neurotensin, substance P and somatostatin was therefore undertaken in human colon using in vitro receptor autoradiography and subtype characterization with receptor-selective ligands. GRP receptors, Y2 receptors, PACAP type1-receptors, cholecystokinin-A receptors, neurotensinl and sst2 receptors were abundantly expressed in the myenteric plexus. Y2, neurotensinl and sst2 receptors were also strongly expressed in the submucosal plexus. Furthermore, expression of GRP receptors, neurokinin (NK)1 receptors, VIP type2-receptors and sst2 receptors was found in the mucosa-directed margin of the circular smooth muscle where the interstitial cells of Cajal are located. A variable and complementary expression of GRP receptors, VIP/PACAP receptors, Y2 neurotensinl, NK1 and somatostatin receptors was found in the circular and longitudinal smooth muscle. NK1 and Y1 receptors were often detected in arteries and veins, while VIP/PACAP and sst2 receptors were found in lymphoid follicles. Y2, VIP type, and sst2 receptors were present in the colonic mucosa. Y2 was strongly expressed in the muscularis mucosae. This study shows that neuropeptide receptors are expressed in high amounts and in highly specific patterns in distinct targets in the human colon, suggesting a major physiological role for these peptides. The data represent the molecular basis to investigate the regulation by neuropeptides of colonic functions and to develop neuropeptide drugs aimed at interacting with these receptors in colonic diseases, such as Hirschsprung's and Crohn's diseases.
Rettenbacher
M
M
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Bern, Switzerland.
Reubi
J C
JC
D001345:Autoradiography; D003106:Colon / Q000033:anatomy & histology / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000033:anatomy & histology / Q000378:metabolism; D009197:Myenteric Plexus / Q000033:anatomy & histology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D013368:Submucous Plexus / Q000033:anatomy & histology / Q000378:metabolism
D009479:Neuropeptides; D018013:Receptors, Neuropeptide