For publication in the Journal of Physiology
We are studying how gastrin regulates the organisation and function of the gastric epithelium. Important target cells for this hormone include the parietal cell, which secretes hydrochloric acid and which requires gastrin for its normal maturation, and the enterochromaffin-like cell which produces and secretes histamine in response to gastrin. We are using genomic and proteomic methods to identify novel proteins that are regulated by gastrin and may mediate these effects. We also examine how gastrin stimulates the release of growth factors, matrix metalloproteinases and protease inhibitors, since it now seems likely that these are important mediators of gastrin-stimulated epithelial cell proliferation, migration and invasion. In these studies extensive use is made of transgenic and gene knock-out models to determine phenotypes in vivo. In the case of CCK, we are studying the expression of the receptor by vagal afferent neurones, and possible interactions at the level of afferent neurones between CCK, and other regulators of food intake including leptin, orexin and ghrelin.