title: Stimulation of gastrin-CCKB receptor promotes migration of gastric AGS cells via multiple paracrine pathways.
abstract: Responses to G protein-coupled receptor stimulation may be mediated by paracrine factors. We have developed a coculture system to study paracrine regulation of migration of gastric epithelial (AGS) cells after stimulation of gastrin-CCK(B) receptors. In cells expressing this receptor, G-17 stimulated migration by activation of protein kinase C. However, G-17 also stimulated the migration of cells expressing green fluorescent protein, but not the receptor, when they were cocultured with receptor-expressing cells consistent with activation of paracrine signals. The use of various pharmacological inhibitors indicated that gastrin stimulated migration via activation of the EGF receptor (EGR-R), the erbB-2 receptor tyrosine kinase, and the MAP kinase pathway. However, gastrin also released fibroblast growth factor (FGF)-1, and migration was inhibited by the FGF receptor tyrosine kinase inhibitor SU-5402. Flow cytometry indicated that in both cell types, gastrin increased MAP kinase via activation of EGF-R but not FGF-R1 or erbB-2. We conclude that gastrin-CCK(B) receptors stimulate epithelial cell migration partly via paracrine mechanisms; transactivation of EGF-R is only one component of the paracrine pathway.
authors.affiliation: Physiological Laboratory, University of Liverpool, United Kingdom.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Noble
authors.forename: Geraint
authors.initials: G
authors.lastname: Wilde
authors.forename: Michael R H
authors.initials: MR
authors.lastname: White
authors.forename: Steven R
authors.initials: SR
authors.lastname: Pennington
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
mesh_terms: D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D005434:Flow Cytometry; D005755:Gastrins / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology*; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013270:Stomach / Q000166:cytology*
chemical_list: D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D016220:Fibroblast Growth Factor 1; D066246:ErbB Receptors; D008666:Metalloendopeptidases