TY - JOUR
T1 - Unique roles of G protein-coupled histamine H 2 and gastrin receptors in growth and differentiation of gastric mucosa
AU - Fukushima, Yasushi
AU - Matsui, Toshimitsu
AU - Saitoh, Toshihito
AU - Ichinose, Masao
AU - Tateishi, Keisuke
AU - Shindo, Takayuki
AU - Fujishiro, Midori
AU - Sakoda, Hideyuki
AU - Shojima, Nobuhiro
AU - Kushiyama, Akifumi
AU - Fukuda, Satoru
AU - Anai, Motonobu
AU - Ono, Hiraku
AU - Oka, Masashi
AU - Shimizu, Yasuhito
AU - Kurihara, Hiroki
AU - Nagai, Ryozo
AU - Ishikawa, Takashi
AU - Asano, Tomoichiro
AU - Omata, Masao
N1 - Funding Information:
This research was supported in part by a grant (to T. Saitoh and T. Ishikawa) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We are grateful to Ms. Masako Fujita, Ms. Kazuyo Shirai and Ms. Manami Ikematsu for helping with our experiments in this study.
PY - 2004/10/19
Y1 - 2004/10/19
N2 - Disruption of histamine H 2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H 2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H 2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H 2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H 2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.
AB - Disruption of histamine H 2 receptor and gastrin receptor had different effects growth of gastric mucosa: hypertrophy and atrophy, respectively. To clarify the roles of gastrin and histamine H 2 receptors in gastric mucosa, mice deficient in both (double-null mice) were generated and analyzed. Double-null mice exhibited atrophy of gastric mucosae, marked hypergastrinemia and higher gastric pH than gastrin receptor-null mice, which were unresponsive even to carbachol. Comparison of gastric mucosae from 10-week-old wild-type, histamine H 2 receptor-null, gastrin receptor-null and double-null mice revealed unique roles of these receptors in gastric mucosal homeostasis. While small parietal cells and increases in the number and mucin contents of mucous neck cells were secondary to impaired acid production, the histamine H 2 receptor was responsible for chief cell maturation in terms of pepsinogen expression and type III mucin. In double-null and gastrin receptor-null mice, despite gastric mucosal atrophy, surface mucous cells were significantly increased, in contrast to gastrin-null mice. Thus, it is conceivable that gastrin-gene product(s) other than gastrin-17, in the stimulated state, may exert proliferative actions on surface mucous cells independently of the histamine H 2 receptor. These findings provide evidence that different G-protein coupled-receptors affect differentiation into different cell lineages derived from common stem cells in gastric mucosa.
KW - Double-null
KW - G protein
KW - Histamine H
KW - mouse
UR - http://www.scopus.com/inward/record.url?scp=5044224471&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2004.09.013
DO - 10.1016/j.ejphar.2004.09.013
M3 - Article
C2 - 15476751
AN - SCOPUS:5044224471
SN - 0014-2999
VL - 502
SP - 243
EP - 252
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -