Guinea-pig ghrelin: its structure, distribution and function in the gastrointestinal tract

Takio Kitazawa, Yuji Okuhara, Hiroyuki Kaiya, Hiroki Teraoka
2018 Proceedings for Annual Meeting of The Japanese Pharmacological Society  
Ghrelin is known to be a 28-amino-acid gastric peptide hormone with a fatty acid modification at the third serine residue, and it has been identified in various vertebrates from cartilaginous fish to mammals. A ghrelin analogue would be a candidate for clinical treatment of gastrointestinal dysmotility. Guinea-pigs are widely used experimental animal for gastrointestinal pharmacology, but ghrelin has not been identified. In this study, we identified guinea-pig ghrelin (gpghrelin), and examined
more » ... he distribution and physiological actions of ghrelin in the guinea-pig. The structure of gp-ghrelin is unique even in mammals and consists of a 28-amino-acid peptide (GASFR SPEHH SAQQR KESRK LPAKI QPR). Seven amino acids are different from those of rat ghrelin at positions 2, 5, 10, 11, 19, 21 and 25, and the third serine residue is modified by n-decanoic acid. Both gp-ghrelin and rat ghrelin increased the intracellular Ca 2+ concentration of HEK293 cells expressing the gp-ghrelin receptor, and the binding affinity of gp-ghrelin was slightly higher than that of rat ghrelin. Gp-ghrelin mRNA was predominantly expressed in the stomach, whereas its expression levels in other organs were low. Immunohistochemical study revealed the presence of ghrelin-immunopositive cells in the gastric mucosa as in other vertebrates. High levels of ghrelin receptor mRNA expression were detected in the pituitary, medulla oblongata and kidney, while moderate levels were found in the thalamus, pons, olfactory bulb, and heart, and the expression levels in other regions including the gastrointestinal tract were very low. Gp-ghrelin and also rat ghrelin did not cause any mechanical responses in isolated gastrointestinal muscle strips (stomach, small intestine and colon) in vitro. Motilin, a family peptide of ghrelin, also did not cause any mechanical changes, and there was no positive correlation between the actions of the two peptides. In conclusion, the N-terminal structure of guinea-pig ghrelin is unique even in mammals, but the binding affinity of gp-ghrelin for the ghrelin receptor is comparable with that of rat ghrelin. Gp-ghrelin did not stimulate motility of guinea-pig gastrointestinal strips in vitro, and that may be due to the low expression level of the ghrelin receptor. Poster session WCP2018
doi:10.1254/jpssuppl.wcp2018.0_po2-6-25 fatcat:hk22n3iikzd5rncsmah6uowvnm