大麻素对大鼠三叉神经节神经元ATP激活电流的抑制作用.pdfVIP

Acta Physiologica Sinica , December 25, 2007, 59 (6): 745-752 745 Research Paper Cannabinoids inhibit ATP-activated currents in rat trigeminal ganglionic neurons 1 1,* 1 1 1 1 1 2 SHEN Jing-Jing , LIU Chang-Jin , LI Ai , HU Xin-Wu , LU Yong-Li , CHEN Lei , ZHOU Ying , LIU Lie-Ju 1Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; 2Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, 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 (CB1 receptor) agonist, reduced ATP-activated current (IATP) significantly. This inhibitory effect was concentration-dependent and was blocked by AM281, a specific CB1 receptor antagonist. Pretreatment with WIN55212-2 at 1×10-13 , 1×10-12 , 1×10-11, 1×10-10 , 1×10-9 -8 -4 and 1×10 mol/L reduced IATP (induced by 1×10 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 IATP pretreated with and without WIN55212-2 showed that WIN55212-2 shifted the curve downward, and decreased the maximal amplitude of IATP by (58.02±4.21)%. But the threshold value and EC50 (1.15×10-4 mol/L vs 1.27×10-4 mol/L) remained unchanged. The inhibition of IATP by WIN55212-2 was reversed by AM281, suggesting that the inhibition was mediated via the CB1 re