The neuronal mechanisms underlying the cardiovascular activities of des-acylated ghrelin (DAG) and ghrelin remain unclear. Not only ghrelin but also DAG that is endocrinically inactive form of ghrelin without binding efficacy to growth-hormone secretagogue receptor type 1a (GHSR-1a) on the pituitary grand exerts cardiovascular actions when microinjected into the rat nucleus tractus solitarius (NTS). These responses may be attributable to a receptor(s) other than GHSR-1a. DAG lacks hydrophobic octanoylation at Ser3 from ghrelin but retains hydrophobicity at Phe4Leu5. We studied the cardiovascular effects in the rat NTS of a synthetic peptide with a hydrophobic-to-hydrophilic substitution at Phe4Leu5 to Ala4Lys5 of DAG(1-10). The intra-NTS microinjection of 80 or 200 pmol/100 nl of the synthetic peptide produced no changes in the rat mean arterial pressure and heart rate. In addition, pretreatment with 200 pmol of the synthetic peptide had no antagonistic effect on the cardiovascular response induced by 80 pmol of DAG or native ghrelin. The synthetic peptide was incapable of evoking hypotensive and bradycardic responses in the NTS. Our results suggest that hydrophobicity at amino acid position 4 to 5 of DAG may be essential to bind a new receptor and to evoke the cardiovascular responses in the NTS. [J Physiol Sci. 2006;56 Suppl:S172]
