School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan; Pathology Research, Safety Research Laboratory, Kissei Pharmaceutical Co., Ltd., 2320-1, Maki, Hotaka, Azumino, Nagano 399-8305, Japan.
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
Peptides. 2018 Jan;99:70-81. doi: 10.1016/j.peptides.2017.11.010. Epub 2017 Nov 26.
We identified guinea pig ghrelin (gp-ghrelin), and examined its distribution and physiological actions in the guinea-pig. Gp-ghrelin is a 28-amino acid peptide (GASFR SPEHH SAQQR KESRK LPAKI QPR); seven amino acids are different from that of rat ghrelin at positions 2, 5, 10, 11, 19, 21, and 25, which include the conserved region known in mammals. The third serine residue is mainly modified by n-decanoyl acid. Both gp-ghrelin and rat ghrelin increased intracellular Ca concentration of HEK293 cells expressing guinea pig growth hormone secretagogue receptor 1a (GHS-R1a), and the affinity of gp-ghrelin was slightly higher than that of rat ghrelin. In addition, gp-ghrelin was also effective in CHO cells expressing rat GHS-R1a with similar affinity to that of rat ghrelin. Gp-ghrelin mRNA was predominantly expressed in the stomach, whereas the expression levels in other organs was low. High levels of GHS-R1a mRNA expression were observed in the pituitary, medulla oblongata, and kidney, while medium levels were noted in the thalamus, pons, olfactory bulb, and heart. Immunohistochemistry identified gp-ghrelin-immunopositive cells in the gastric mucosa and pancreas. Intraperitoneal injection of gp-ghrelin increased food intake in the guinea pig. Gp-ghrelin did not cause any mechanical responses in isolated gastrointestinal smooth muscles in vitro, similar to rat ghrelin. In conclusion, the N-terminal structures that are conserved in mammals were different in gp-ghrelin. Moreover, the functional characteristics of gp-ghrelin, other than its distribution, were dissimilar from those in other Rodentia.
我们鉴定了豚鼠 ghrelin（gp-ghrelin），并研究了其在豚鼠中的分布和生理作用。gp-ghrelin 是一种 28 个氨基酸的肽（GASFR SPEHH SAQQR KESRK LPAKI QPR）；在 2、5、10、11、19、21 和 25 位有 7 个氨基酸与大鼠 ghrelin 不同，其中包括在哺乳动物中已知的保守区域。第三个丝氨酸残基主要被 n-癸酰酸修饰。gp-ghrelin 和大鼠 ghrelin 均可增加表达豚鼠生长激素促分泌素受体 1a（GHS-R1a）的 HEK293 细胞内 Ca2+浓度，且 gp-ghrelin 的亲和力略高于大鼠 ghrelin。此外，gp-ghrelin 在表达大鼠 GHS-R1a 的 CHO 细胞中也有效，与大鼠 ghrelin 的亲和力相似。gp-ghrelin mRNA 主要在胃中表达，而在其他器官中的表达水平较低。GHS-R1a mRNA 表达水平在垂体、延髓和肾脏中较高，在丘脑、脑桥、嗅球和心脏中中等。免疫组织化学鉴定出胃黏膜和胰腺中有 gp-ghrelin 免疫阳性细胞。腹腔内注射 gp-ghrelin 可增加豚鼠的食物摄入量。gp-ghrelin 与大鼠 ghrelin 相似，在体外不会引起胃肠道平滑肌的任何机械反应。总之，gp-ghrelin 的 N 端结构在哺乳动物中是保守的，但不同。此外，gp-ghrelin 的功能特征除了分布不同外，与其他啮齿动物也不同。
