title: GHRP-6 mimics ghrelin-induced stimulation of food intake and suppression of locomotor activity in goldfish.
abstract: Ghrelin was first identified and characterized from rat stomach as an endogenous ligand for the growth hormone secretagogue (GHS) receptor (GHS-R). Ghrelin also acts as an orexigenic factor and regulates energy balance in rodents. In goldfish, native ghrelin consists of 11 molecular variants, the major form being a 17-residue peptide with n-octanoic acid modification (n-octanoyl ghrelin17), and intraperitoneal (IP) administration of n-octanoyl ghrelin17 induces central actions such as stimulation of food intake and suppression of locomotor activity through capsaicin-sensitive afferents. Four types of GHS-Rs (1a-1, 1a-2, 2a-1 and 2a-2) have been identified in goldfish, and one GHS, GHRP-6, can activate only GHS-R2a-1 in vitro. However, there is no information about the effect of GHRP-6 on food intake and locomotor activity in goldfish in vivo. Therefore, in the present study, we examined whether IP-administered GHRP-6 would mimic the orexigenic action of n-octanoyl ghrelin17 and its suppression of locomotor activity. IP administration of GHRP-6 at 1pmol/g body weight (BW) stimulated food intake, and was equipotent to the orexigenic action of n-octanoyl ghrelin17 at 10 pmol/g BW. IP-injected GHRP-6 at 1 pmol/g BW also induced a significant decrease of locomotor activity, as was the case for IP-injected n-octanoyl ghrelin17 at 10 pmol/g BW. The action of GHRP-6 was blocked by IP-preinjected capsaicin at 160 nmol/g BW. These results suggest that the central action of GHRP-6 might be mediated via the GHS-R2a-1-signaling pathway, and subsequently through capsaicin-sensitive afferents in goldfish.
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama 930-8555, Japan.
authors.forename: Satowa
authors.initials: S
authors.lastname: Yahashi
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kaiya
authors.forename: Kouhei
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage* / Q000502:physiology; D006054:Goldfish / Q000502:physiology*; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000502:physiology; D054440:Receptors, Ghrelin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D002211:Capsaicin