1.Physiological evidence for interaction between the HIV-1 co-receptor CXCR4 and the cannabinoid system in the brain.
Benamar K1, Yondorf M, Geller EB, Eisenstein TK, Adler MW. Br J Pharmacol. 2009 Aug;157(7):1225-31. doi: 10.1111/j.1476-5381.2009.00285.x. Epub 2009 Jun 22.
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.
2.Intrahypothalamic injection of the HIV-1 envelope glycoprotein induces fever via interaction with the chemokine system.
Benamar K1, Addou S, Yondorf M, Geller EB, Eisenstein TK, Adler MW. J Pharmacol Exp Ther. 2010 Feb;332(2):549-53. doi: 10.1124/jpet.109.160309. Epub 2009 Nov 11.
Wasting syndrome is a common complication of HIV infection and is marked by progressive weight loss and weakness, often associated with fever. The mechanisms involved in the pathogenesis of these syndromes are not well defined, and neither are the brain areas involved. The present study tests a new hypothesis: that the preoptic anterior hypothalamus (POAH), the main brain area for thermoregulation and fever, has a role in the pathogenesis of fever induced by glycoprotein 120 (gp120), the surface envelope protein used by the HIV to gain access into immune cells, and that the CXC chemokine receptors (CXCR4) that serve as a coreceptor for HIV entry mediate the effect. A sterilized stainless steel C313G cannula guide was implanted into the POAH, and a biotelemetry system was used to monitor the body temperature (Tb) changes. The administration of gp120 into the POAH induced fever in a dose-dependent manner. To demonstrate possible links between the gp120 and CXCR4 in generating the fever, we pretreated the rats with 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] octohydrobromide dihydrate (AMD 3100), an antagonist of stromal cell-derived growth factor (SDF)-1alpha/CXCL12, acting at its receptor, CXCR4, 30 min before administration of gp120.
