Behavioural and biological effects of des-Gln14-ghrelin
Roberta Dochnal, Mónika Mácsai & Gyula Szabó
Ghrelin, ligand for the growth hormone secretagogue receptor (GHS-R), was isolated from the stomach. Immunoreactive neurons were observed in the hypothalamic nuclei and the ependymal layer of the third ventricle. Lower amounts are produced in the small intestine, pancreas, liver, kidney, placenta, and pituitary. Receptors have widespread distribution in the body, mainly concentrated in the hypothalamus-pituitary unit.
Ghrelin, a 28-amino acid peptide, has an n-octanoyl modification at its third serine residue. This modification is necessary for biologic activity. A second endogenous ghrelin form was discovered which is derived from an alternative splicing of the ghrelin gene. This 27 amino acid peptide is called des-Gln14-ghrelin, and has an n-octanoyl modification at its third serine residue, identical to ghrelin, except for deletion of one glutamine.
Considerable amount of data has accumulated regarding biological effects of ghrelin 28 but des-Gln14-ghrelin was less studied. No experiment investigating behavioral effects of des-Gln14-ghrelin has been carried out in mice. Therefore in the present study we aimed to elucidate how des-Gln14-ghrelin influences locomotion, anxiety, body temperature, and pain threshold in CFLP mice. The peptide was injected intracerebroventicularly (icv.) and we performed open-field, plus-maze, and tail flick tests.
Our experiments showed that des-Gln14-ghrelin increased locomotion and exploratory behavior. The most effective dose was 2 μg/μl, which induced a significant increase in both the vertical and horizontal locomotor activity in the open field test. The increased locomotion was confirmed by the plus maze test also, where the number of entries was increased. In addition, the peptide in higher doses (4 μg/μl) seems to induce anxiolytic effect. Lower doses did not change the anxiety level. Analgesia and body temperature seems to be influenced by des-Gln14-ghrelin, but our results were not statistically significant.
This work was supported by ETT (050/2003), NKFP (1/027/2001), OTKA (T043095).