Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain
Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain
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DOI：
10.1111/j.1476-5381.2009.00285.x
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发表时间：
2009-08-01
影响因子：
7.3
通讯作者：
Adler, Martin W.
中科院分区：
文献类型：
--
作者：
Benamar, Khalid;Yondorf, Menachem;Adler, Martin W.
背景与目的：趋化因子基质细胞衍生生长因子-1 α（stromal cell derived growth factor-1 alpha，SGF-1 alpha）是一种重要的细胞因子，CXC趋化因子家族的成员SDF-1 α/CXCL 12和参与人类免疫缺陷病毒-1（HIV-1）进入的共受体CXCR 4的配体，被测试其与对大麻素的生理反应的可能相互作用。（4，5-二氢-2-甲基-4-（4-吗啉基甲基）-1-（1-萘基-羰基）-6H-吡咯并[3，2，1 ij]喹啉-6-酮]直接注入视前区前下丘脑（POAH），这是参与体温调节的主要脑区。WIN 55，212 -2（5-15 μ g）诱发剂量相关的体温降低，其被直接显微注射到POAH中的SDF-1 α/CXCL 12减弱。SDF-1 alpha/CXCL 12对WIN 55，212 -2诱导的体温降低的抑制作用可被SDF-1 alpha/CXCL 12的拮抗剂1，1 '-[1，4-亚苯基双（亚甲基）]双[1，4，8，1,1-四氮杂环十四烷]-氢溴酸盐二水合物逆转，该拮抗剂作用于其受体CXCR 4。
Background and purpose:The chemokine, stromal cell-derived growth factor-1 alpha (SDF-1 alpha/CXCL12), a member of the CXC chemokine family, and the ligand for CXCR4, the co-receptor involved in the entry of human immunodeficiency virus-1 (HIV-1), was tested for its possible interaction with a physiological response to a cannabinoid.Experimental approach:The cannabinoid agonist, an aminoalkylindole, (+)-WIN 55,212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], was infused directly into the preoptic anterior hypothalamus (POAH), the primary brain area involved in thermoregulation.Key results:WIN 55,212-2 (5-15 mu g) evoked a dose-related hypothermia, which was attenuated by SDF-1 alpha/CXCL12 microinjected directly into the POAH. The inhibitory effect of SDF-1 alpha/CXCL12 on WIN 55,212-2-induced hypothermia was reversed by 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] octohydrobromide dihydrate, an antagonist of SDF-1 alpha/CXCL12, acting at its receptor, CXCR4.Conclusion and implications:This study provides the first in vivo evidence for a thermoregulatory interaction between the HIV-1 co-receptor and the cannabinoid system in the brain.