Differentiation of gastric ECL cells is altered in CCK(2) receptor-deficient mice.
OBJECTIVE
Gastrin stimulation of the type 2 cholecystokinin (CCK(2)) receptor results in ECL cell proliferation and histamine secretion. This report describes the effects of targeted disruption of the CCK(2) receptor gene on ECL cell morphology and function.


METHODS
The ECL cells in the oxyntic mucosa of CCK(2) receptor-deficient (knockout [KO]) vs. wild-type (WT) mice were investigated by immunocytochemical and biochemical approaches, as well as by electron microscopy.


RESULTS
Immunocytochemistry demonstrates similar numbers (cells per millimeter of horizontal length of mucosa) of pancreastatin- or vesicle monoamine transporter-2 (VMAT-2)-immunoreactive cells in WT mice and KO mice. However, only WT mice harbor histamine-immunoreactive ECL cells. The mucosal histamine content in KO mice (likely originating from mast cells) is only a minute fraction of that present in WT animals. The activity of the histamine forming enzyme, histidine decarboxylase (a marker of ECL cells), was undetectable in the oxyntic mucosa of KO mice yet was readily apparent in the mucosa from WT animals. Electron microscopy revealed numerous ECL cells in WT mice. In KO animals, these cells were replaced by an "ECL-like" cell type, characterized by a lack of secretory vesicles (a hallmark feature of normal ECL cells) and the presence of dense-core granules and microvesicles in numbers comparable to those found in WT ECL cells. Based on ultrastructural features, the ECL-like cells in KO mice can be readily distinguished from other gastric endocrine cells, including A-like cells and D cells.


CONCLUSIONS
Absence of a single gene product, the CCK(2) receptor, alters the differentiation and function of gastric ECL cells.
Chen
Duan
D
Department of Intra-abdominal Diseases and Laboratory Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Duan.Chen@medisin.ntnu.no
Zhao
Chun-Mei
CM
Al-Haider
Wisam
W
Håkanson
Rolf
R
Rehfeld
Jens F
JF
Kopin
Alan S
AS
D000818:Animals; D002454:Cell Differentiation; D019861:Enterochromaffin-like Cells / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology*; D005755:Gastrins / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology*
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin