Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-Terminally Extended Hemopressin Peptide

doi:10.1124/jpet.113.209866

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	Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-Terminally Extended Hemopressin Peptide
	Han, ZL; Fang, Q; Wang, ZL; Li, XH; Li, N; Chang, XM; Pan, JX; Tang, HZ; Wang, R; Wang, R (reprint author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Peoples R China.
刊名	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
	2014-02
卷号	348 期号:2 页码:316-323
ISSN号	0022-3565
DOI	10.1124/jpet.113.209866
文献子类	Article
英文摘要	The cannabinoid system has been demonstrated to modulate the acute and chronic pain of multiple origins. Mouse VD-hemopressin (alpha) [(m)VD-Hp alpha], an 11-residue a-hemoglobin-derived peptide, was recently reported to function as a selective agonist of the cannabinoid receptor type 1 (CB1) in vitro. To characterize its behavioral and physiological properties, we investigated the in vivo effects of (m) VD-Hpa in mice. In the mouse tail-flick test, (m)VD-Hp alpha dose-dependently induced antinociception after supraspinal (EC50 = 6.69 nmol) and spinal (EC50 = 2.88 nmol) administration. The antinociceptive effects of (m)VD-Hp alpha (intracerebroventricularly and intrathecally) were completely blocked by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)4- methyl-1H-pyrazole-3-carboxamide (AM251; CB1 antagonist), but not by 6-iodo-2-methyl-1-[ 2-(4-morpholinyl) ethyl]-1H-indol-3-yl (4-methoxyphenyl)-methanone (AM630; CB2 antagonist) or naloxone (opioid antagonist), showing its selectivity to the CB1 receptor. Furthermore, the central nervous system (CNS) effects of (m)VD-Hp alpha were evaluated in body temperature, locomotor activity, tolerance development, reward, and food intake assays. At the highly antinociceptive dose (3 x EC50), (m)VD-Hp alpha markedly exerted hypothermia and hypoactivity after supraspinal administration. Repeated intracerebroventricular injection of (m)VD-Hp alpha resulted in both development of tolerance to antinociception and conditioned place aversion. In addition, central injection of (m)VD-Hp alpha dose-dependently stimulated food consumption. These findings demonstrate that this novel cannabinoid peptide agonist induces CB1-mediated central antinociception with some CNS effects, which further supports a CB1 agonist character of (m)VD-Hp alpha. Moreover, the current study will be helpful to understand the in vivo properties of the endogenous peptide agonist of the cannabinoid CB1 receptor.
学科主题	Pharmacology & Pharmacy
出版地	BETHESDA
资助项目	国家自然科学基金项目 ; 国家科技重大专项 ; 长江学者和创新团队发展计划 ; 中央高校基本科研业务费专项资金
项目编号	National Natural Science Foundation of China [81273355, 91213302] ; Key National S&T Program of the Ministry of Science and Technology Grant [2012ZX09504001-003] ; Program for Changjiang Scholars and Innovative Research Team in University [IRT1137] ; Fundamental Research Funds for the Central Universities
语种	英语
WOS记录号	WOS:000329911800011
资助机构	NSFC ; MOST ; MOE ; LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/121674]
专题	基础医学院_期刊论文
通讯作者	Wang, R (reprint author), Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 199 Donggang West Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Han, ZL,Fang, Q,Wang, ZL,et al. Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-Terminally Extended Hemopressin Peptide[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2014,348(2):316-323.
APA	Han, ZL.,Fang, Q.,Wang, ZL.,Li, XH.,Li, N.,...&Wang, R .(2014).Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-Terminally Extended Hemopressin Peptide.JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,348(2),316-323.
MLA	Han, ZL,et al."Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-Terminally Extended Hemopressin Peptide".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 348.2(2014):316-323.