Enhanced ghrelin expression and subsequent acid secretion in mice with genetic H(2)-receptor knockout.
BACKGROUND
Ghrelin, an appetite-promoting peptide secreted from the stomach, is reported to enhance preprandial acid output, possibly through stimulation of the cephalic phase. The present study was designed to clarify the dynamics of ghrelin in H(2) receptor (H(2)R)-null mice by genetic H(2)R knockout.


METHODS
Fifteen-week- and 54-week-old H(2)R-null mice and their littermates were used. After evaluating the levels of food intake and body-weight increments, mice were killed, and the plasma and gastric active and total ghrelin levels were examined by radioimmunoassay, and gastric preproghrelin mRNA expression was examined by quantitative reverse transcriptase-polymerase chain reaction. Furthermore, each stomach specimen was evaluated by immunohistochemistry and transmission electron microscopy for ghrelin.


RESULTS
The levels of food intake and body-weight gain of the H(2)R-null mice were higher than those of wild-type mice. The gastric pH of the 54-week-old H(2)R-null mice was lower than that of the 15-week-old mice. Gastric preproghrelin mRNA expression, plasma ghrelin level, and density of ghrelin-immunoreactive cells in the gastric mucosa of the H(2)R-null mice were significantly increased compared with those of the wild-type mice. Ghrelin-positive immunogold density seen in the electron micrograph was significantly reduced in A-like cells of the H(2)R-null mouse stomach.


CONCLUSIONS
Ghrelin production and secretion from A-like cells in the gastric fundus are upregulated in H(2)R-null mice, a genetic H(2)R knockout model.
Arakawa
Mamoru
M
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Suzuki
Hidekazu
H
Minegishi
Yuriko
Y
Fukushima
Yasushi
Y
Masaoka
Tatsuhiro
T
Ishikawa
Takashi
T
Hosoda
Hiroshi
H
Kangawa
Kenji
K
Hibi
Toshifumi
T
D000818:Animals; D001835:Body Weight / Q000502:physiology; D004759:Enterochromaffin Cells / Q000378:metabolism* / Q000648:ultrastructure; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D015870:Gene Expression; D054439:Ghrelin / Q000096:biosynthesis / Q000235:genetics*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054439:Ghrelin; D006635:Histamine H2 Antagonists; D012333:RNA, Messenger