title: Study on the molecular mechanism of antinociception induced by ghrelin in acute pain in mice.
abstract: Ghrelin has been identified as the endogenous ligand for the GHS-R1α (growth hormone secretagogue receptor 1 alpha). Our previous experiments have indicated that ghrelin (i.c.v.) induces antinociceptive effects in acute pain in mice, and the effects were mediated through the central opioid receptors and GHS-R1α. However, which opioid receptor (OR) mediates the antinociceptive effects and the molecular mechanisms are also needed to be further explored. In the present study, the antinociceptive effects of ghrelin (i.c.v.) could be fully antagonized by δ-opioid receptor antagonist NTI. Furthermore, the mRNA and protein levels of δ-opioid peptide PENK and δ-opioid receptor OPRD were increased after i.c.v injection of ghrelin. Thus, it showed that the antinociception of ghrelin was correlated with the GHS-R1α and δ-opioid receptors. To explore which receptor was firstly activated by ghrelin, GHS-R1α antagonist [D-Lys(3)]-GHRP-6 was co-injection (i.c.v.) with deltorphin II (selective δ-opioid receptor agonist). Finally, the antinociception induced by deltorphin II wasn't blocked by the co-injection (i.c.v.) of [D-Lys(3)]-GHRP-6, indicating that the GHS-R1α isn't on the backward position of δ-opioid receptor. The results suggested that i.c.v. injection of ghrelin initially activated the GHS-R1α, which in turn increased the release of endogenous PENK to activation of OPRD to produce antinociception.
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Fu-Yan
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.affiliation: Medical Experimental Teaching Department, Nanchang University, Nanchang 330031, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China. Electronic address: jwei@ncu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
mesh_terms: D059787:Acute Pain / Q000188:drug therapy* / Q000473:pathology; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D054439:Ghrelin / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000008:administration & dosage; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000700:Analgesics; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; C114628:NTI compound; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D017465:Receptors, Opioid, delta; C059567:deltorphin; D009271:Naltrexone; D009020:Morphine
keywords: Antinociception; GHS-R1α; Ghrelin; Opioid receptors; Protein expression; Transcriptional expression