title: Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice.
abstract: Neuropeptide FF (NPFF) system has recently been reported to modulate cannabinoid-induced antinociception. The aim of the present study was to further investigate the roles of NPFF system in the antinociceptive effects induced by intracerebroventricular (i.c.v.) administration of mouse VD-hemopressin(α), a novel endogenous agonist of cannabinoid CB1 receptor, in naive and VD-hemopressin(α)-tolerant mice. The effects of NPFF system on the antinociception induced by VD-hemopressin(α) were investigated in the radiant heat tail-flick test in naive mice and VD-hemopressin(α)-tolerant mice. The cannabinoid-tolerant mice were produced by given daily injections of VD-hemopressin(α) (20 nmol, i.c.v.) for 5 days and the antinociception was measured on day 6. In naive mice, intracerebroventricular injection of NPFF dose-dependently attenuated central analgesia of VD-hemopressin(α). In contrast, neuropeptide VF (NPVF) and D.NP(N-Me)AFLFQPQRF-NH2 (dNPA), two highly selective agonists for Neuropeptide FF1 and Neuropeptide FF2 receptors, enhanced VD-hemopressin(α)-induced antinociception in a dose-dependent manner. In addition, the VD-hemopressin(α)-modulating activities of NPFF and related peptides were antagonized by the Neuropeptide FF receptors selective antagonist 1-adamantanecarbonyl-RF-NH2 (RF9). In VD-hemopressin(α)-tolerant mice, NPFF failed to modify VD-hemopressin(α)-induced antinociception. However, both neuropeptide VF and dNPA dose-dependently potentiated the antinociception of VD-hemopressin(α) and these cannabinoid-potentiating effects were reduced by RF9. The present works support the cannabinoid-modulating character of NPFF system in naive and cannabinoid-tolerant mice. In addition, the data suggest that a chronic cannabinoid treatment modifies the pharmacological profiles of NPFF, but not the cannabinoid-potentiating effects of neuropeptide VF and dNPA.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Pan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Zi-Long
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Tang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Yu
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address: fangq@lzu.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D000700:Analgesics; D004151:Dipeptides; D009479:Neuropeptides; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C586692:VDPVNFKLLSH-OH; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C000611306:dNPA peptide; C083929:neuropeptide FF receptor; C503959:neuropeptide VF; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000218:Adamantane
keywords: 1DMe (PubChem CID: 71345956); 2-arachidonoylglycerol (PubChem CID: 5282280); Antinociception; Cannabinoids; Hemopressin (PubChem CID: 71312009); Hu-210 (PubChem CID: 9821569); Mice; NPFF (PubChem CID: 123797); Neuropeptide FF; Neuropeptide VF (PubChem CID: 71451611); RF9 (PubChem CID: 53320361); RVD-hemopressin(α) (PubChem CID: 90488874); Tolerance; VD-hemopressin(α); WIN55,212-2 (PubChem CID: 6604176); Δ(9)-tetrahydrocannabinol (PubChem CID: 16078)