Abstract
Studies to characterize the endogenous expression and pharmacology of peripheral human cannabinoid receptor (hCB2) have been hampered by the dearth of authentic anti-hCB2 antibodies and the lack of radioligands with CB2 selectivity. We recently described a novel CB2 inverse agonist, N-[1(S)-[4-[[4-methoxy-2-[(4methoxyphenyl)sulfonyl] phenyl]sulfonyl] phenyl]ethyl]methane-sulfonamide (Sch225336), that binds hCB2 with high affinity and excellent selectivity versus hCB1. The precursor primary amine of Sch225336 was prepared and reacted directly with [(35)S]mesyl chloride (synthesized from commercially obtained [(35)S]methane sulfonic acid) to generate [(35)S]Sch225336. [(35)S]Sch225336 has high specific activity (>1,400 Ci/mmol) and affinity for hCB2 (65 pm). Using [(35)S]Sch225336, we assayed hemopoietic cells and cell lines to quantitate the expression and pharmacology of hCB2. Lastly, we used [(35)S]Sch225336 for detailed autoradiographic analysis of CB2 in lymphoid tissues. Based on these data, we conclude that [(35)S]Sch225336 represents a unique radioligand for the study of CB2 endogenously expressed in blood cells and tissues.
Highlights
THP-1, U937, and leukemia EoL-1 cells as well as human monocytes, eosinophils, and dendritic cells [2,3,4]
Direct measurement of human CB2 (hCB2) protein expression in immune cells has been hampered by the lack of radioligands with CB2 selectivity and high specific activity
We described a novel CB2 inverse agonist, N-[1(S)-[4-[[4-methoxy-2-[(4methoxyphenyl)sulfonyl]phenyl]sulfonyl]phenyl]ethyl] methanesulfonamide, that binds hCB2 with picomolar affinity and has excellent selectivity versus hCB1 [6]
Summary
THP-1, U937, and leukemia EoL-1 cells as well as human monocytes, eosinophils, and dendritic cells [2,3,4]. Direct measurement of hCB2 protein expression in immune cells has been hampered by the lack of radioligands with CB2 selectivity and high specific activity.
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