Arakawa Mamoru, Suzuki Hidekazu, Minegishi Yuriko, Fukushima Yasushi, Masaoka Tatsuhiro, Ishikawa Takashi, Hosoda Hiroshi, Kangawa Kenji, Hibi Toshifumi
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
J Gastroenterol. 2007 Sep;42(9):711-8. doi: 10.1007/s00535-007-2084-2. Epub 2007 Sep 25.
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.
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.
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.
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.
胃泌素释放肽（ghrelin）是一种由胃分泌的促进食欲的肽，据报道它可能通过刺激头期来增加餐前胃酸分泌。本研究旨在通过基因敲除H2受体（H2R）来阐明H2R基因敲除小鼠中胃泌素释放肽的动态变化。
使用15周龄和54周龄的H2R基因敲除小鼠及其同窝小鼠。在评估食物摄入量和体重增加水平后，处死小鼠，通过放射免疫分析法检测血浆和胃中活性及总胃泌素释放肽水平，并通过定量逆转录聚合酶链反应检测胃前胃泌素释放肽mRNA表达。此外，通过免疫组织化学和透射电子显微镜对每个胃标本进行胃泌素释放肽评估。
H2R基因敲除小鼠的食物摄入量和体重增加水平高于野生型小鼠。54周龄H2R基因敲除小鼠的胃pH低于15周龄小鼠。与野生型小鼠相比，H2R基因敲除小鼠胃黏膜中的胃前胃泌素释放肽mRNA表达、血浆胃泌素释放肽水平和胃泌素释放肽免疫反应性细胞密度显著增加。在H2R基因敲除小鼠胃的A样细胞中，电子显微镜下可见的胃泌素释放肽阳性免疫金密度显著降低。
在H2R基因敲除小鼠（一种基因敲除H2R的模型）中，胃底A样细胞中胃泌素释放肽的产生和分泌上调。
