Ghrelin is a peripheral peptide hormone, which is involved in the regulation of energy homeostasis, regulation of food intake and secretion of growth hormone. Searching for the ghrelin receptor antagonist is one way of finding a new lead compounds in order to treat conditions, such as overweight, obesity and its other related illness conditions. Department of Pharmaceutical Biology, Faculty of Pharmacy of University of Ljubljana has developed new peptide ligands of the ghrelin receptor with the help of bacteriophage imaging technology, which have expressed in vitro antagonistic activity. In the master’s thesis we have tested the most effective peptide ligand among them (peptide P1) in vivo study on the C57BL/6J mouse model strain. The activity of peptide, which we have named P1, was compared with the known ghrelin antagonist [D-Lys-3] -GHRP-6. In our thesis we have tested two methods of applying substances, through abdominal and nasal cavity. We conducted 3 experiments; in experiments 1 and 2 we have monitored the food intake depending on the different application of substances. In the experiment 3, we have monitored the concentration of growth hormone in the serum of the tested animals after intraperitoneal application. In experiments 1 and 2 we had three testing groups of animals; 1) a control group, 2) group with the addition of [D-Lys-3]-GHRP-6 and 3) the group with added peptide P1. In experiment 3, additional three testing groups were added to the experiment: 4) group with the addition of ghrelin, 5) with simultaneously appliedghrelin and peptide P1 and 6) with simultaneously applied [D-Lys-3]-GHRP-6 and peptide P1.
Ad libitum food intake after 30 min from intraperitoneal application was distinguished between control group and group with [D-Lys-3] - GHRP-6, while no expected changes were noticed in the group with added peptide P1. Differences were also observed in the concentration of serum growth hormone. The application of ghrelin has, in comparison with the carrier (control group), significantly increased expression of growth hormone in the serum. Simultaneous application of ghrelin and peptide P1 resulted in an unexpectedly higher growth hormone concentration than the application of ghrelin itself. The results of our study did not confirm the antagonistic in vivo activity of peptide P1 on the food intake, but they showed effect of peptide P1 on the secretion of growth hormone release.