학술논문

Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain.
Document Type
Journal Article
Source
British Journal of Pharmacology. Aug2009, Vol. 157 Issue 7, p1225-1231. 7p.
Subject
*CANNABINOIDS
*HIV infections
*CELL receptors
*BRAIN physiology
*CHEMOKINES
*GROWTH factors
*BODY temperature regulation
*HYPOTHALAMUS
Language
ISSN
0007-1188
Abstract
Background and Purpose: The chemokine, stromal cell-derived growth factor-1alpha (SDF-1alpha/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 microg) evoked a dose-related hypothermia, which was attenuated by SDF-1alpha/CXCL12 microinjected directly into the POAH. The inhibitory effect of SDF-1alpha/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-1alpha/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. [ABSTRACT FROM AUTHOR]