title: Gene expression profiling of gastric mucosa in mice lacking CCK and gastrin receptors.
abstract: The stomach produces acid, which may play an important role in the regulation of bone homeostasis. The aim of this study was to reveal signaling pathways in the gastric mucosa that involve the acid secretion and possibly the bone metabolism in CCK1 and/or CCK2 receptor knockout (KO) mice. Gastric acid secretion was impaired and the ECL cell signaling pathway was inhibited in CCK2 receptor KO mice but not in CCK1 receptor KO mice. However, in CCK1+2 receptor double KO mice the acid secretion in response to pylorus ligation-induced vagal stimulation and the ECL cell pathway were partially normalized, which was associated with an up-regulated pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1). The basal part of the gastric mucosa expressed parathyroid hormone-like hormone (PTHLH) in a subpopulation of likely ECL cells (and possibly other cells) and vitamin D3 1α hydroxylase probably in trefoil peptide2-immunoreactive cells. In conclusion, mice lacking CCK receptors exhibited a functional shift from the gastrin-CCK pathways to the neuronal pathway in control of the ECL cells and eventually the acid secretion. Taking the present data together with previous findings, we suggest a possible link between gastric PTHLH and vitamin D and bone metabolism.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway. Electronic address: chun-mei.zhao@ntnu.no.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Zhao
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
authors.forename: Arnar
authors.initials: A
authors.lastname: Flatberg
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
authors.forename: Vidar
authors.initials: V
authors.lastname: Beisvag
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
authors.forename: Bård
authors.initials: B
authors.lastname: Kulseng
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway; Department of Gastrointestinal and Liver Diseases, St. Olav's University Hospital, 7006 Trondheim, Norway.
authors.forename: Arne K
authors.initials: AK
authors.lastname: Sandvik
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100 København Ø, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
authors.forename: Duan
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D043886:Receptor, Cholecystokinin A / Q000172:deficiency* / Q000235:genetics; D043887:Receptor, Cholecystokinin B / Q000172:deficiency* / Q000235:genetics
chemical_list: D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B
keywords: CCK receptors; Gastric acid secretion; Mice; Stomach–bone axis