Relative involvement of cannabinoid CB 1 and CB 2 receptors in the Δ9-tetrahydrocannabinol-induced inhibition of natural killer activity

Abstract

We demonstrated that in vivo administration of Δ 9-tetrahydrocannabinol in mice (15 mg/kg s.c.) significantly inhibited natural killer cell (NK) cytolytic activity without affecting Concanavalin A (ConA)-induced splenocyte proliferation. Moreover, we investigated the effect of in vivo pretreatment with cannabinoid receptor antagonists, namely, the selective cannabinoid CB 1 receptor antagonist SR 141716 [ N-piperidin-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide] and the selective cannabinoid CB 2 receptor antagonist SR 144528 { N-[(1 S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide}, on Δ 9-tetrahydrocannabinol-induced inhibition of NK cytolytic activity. Both antagonists partially reversed the Δ 9-tetrahydrocannabinol inhibition of NK cytolytic activity, although the cannabinoid CB 1 receptor antagonist was more effective than the cannabinoid CB 2 receptor antagonist. The parallel measurement of interferon γ and interleukin 2 levels revealed that Δ 9-tetrahydrocannabinol significantly reduced (about 70%) the former cytokine without affecting the latter. Cannabinoid CB 1 and CB 2 receptor antagonists completely reversed the interferon γ reduction induced by Δ 9-tetrahydrocannabinol. Our results indicate that both types of cannabinoid receptors are involved in the complex network mediating NK cytolytic activity.