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Cannabinoids inhibit ATP--activated currents in rat trigeminal ganglionic neurons

Shen Jingjing, Liu Changjin, Li Ai, Hu Xinwu, Lu Yongli, Chen Lei, Zhou Ying, Liu Lieju

Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology.Wuhan 430030,Hubei；USA

Abstract

The present study aimed to investigate whether cannabinoids could modulate the response mediated by ATP receptor （P2X purinoceptor）. Whole-cell patch-clamp recording was performed on cultured rat trigeminal ganglionic （TG） neurons. The majority of TG neurons were sensitive to ATP （67/75, 89.33%）. Extracellular pretreatment with WIN55212-2, a cannabinoid receptor 1 （CB 1 receptor） agonist, reduced ATP-activated current （I_(ATP)） significantly. This inhibitory effect was concentration-dependent and was blocked by AM281, a specific CB 1 receptor antagonist. Pretreatment with WIN55212-2 at 1×10~(-13), 1×10~(-12), 1×10~(-11), 1×10~(-10), 1×10~(-9) and 1×10~(-8) mol/L reduced I_(ATP) （induced by 1×10~(-4) mol/L ATP） by （8.14±3.14）%, （20.11±2.72）%, （46.62±3.51）%, （72.16±5.64）%, （80.21±2.80）% and （80.59±3.55）%, respectively. The concentration-response curves for I_(ATP) pretreated with and without WIN55212-2 showed that WIN55212-2 shifted the curve downward, and decreased the maximal amplitude of I_(ATP) by （58.02±4.21）%. But the threshold value and EC_(50) （1.15×10~(-4) mol/L vs 1.27×10~(-4) mol/L） remained unchanged. The inhibition of I_(ATP) by WIN55212-2 was reversed by AM281, suggesting that the inhibition was mediated via the CB 1 receptor. Pretreatment with forskolin [an agonist of adenylyl cyclase （AC）] or 8-Br-cAMP reversed the inhibition of I_(ATP) by WIN55212-2. These results suggest that the inhibitory effect of cannabinoids on I_(ATP) is mediated via the CB 1 receptors, that lead to inhibition of the AC-cAMP-PKA signaling pathway.

Key words: cannabinoid receptor 1;WIN55212-2;P2X receptor;trigeminal ganglion;patch-clamp technique

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Citing This Article：

Shen Jingjing, Liu Changjin, Li Ai, Hu Xinwu, Lu Yongli, Chen Lei, Zhou Ying, Liu Lieju. Cannabinoids inhibit ATP--activated currents in rat trigeminal ganglionic neurons. Acta Physiol Sin 2007; 59 (6): 745-752 (in Chinese with English abstract).