大麻素抑制大鼠三叉神经节神经元ATP激活电流.pdfVIP

Acta Physiologica Sinica，December 25，2007，59(6)：745·752 745 http：／／www．actaps．com．ca Cannabinoids inhibit ATP-activated currents in rat trigeminal ganglionic SHEN Jing—Jing ，LIU Chang-Jin ’，LI Ai ，HU Xin—Wu ，LU Yong—Li ，CHEN Lei ，ZHOUⅥng ，LIU Lie-Ju lDepartment ofP siology,Tongji Medical College．Huazhong University ofScience and Technology,Wuhan 43003~China； Departments ofAnesthesiology and Neurobiology，Duke University Medical Center,Durham，Noah Carolina 27710,USA Abstract：The present study aimed to investigate whether cannabinoids could modulate the response me~ated 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(1Aav)significantly．This inhibitory effect was concentration·dependent and was blocked by AM281，a specific CB1 receptor antagonist．Pretreatment with WIN55212—2 at lxl0‘”，lx10’ ，lx10‘“，lx10‘ ，lx10‘ and lx10 mol／L reduced厶TP(induced by lx10。mol／LATP)by(8．14~3．14)％，(20．11~2．72)％，(46．62~3．51)％，(72．16~5．64)％， (8O．21~2．80)％and(8O．59~3．55)％，respectively．The concentration·response curves for rP pretreated with and without WIN55212·2 showed that WIN55212·2 shifted the curve downward，and decreased the maximal amplitude of J^TP by(58．02~4．21)％．But the threshold value and EC n(1．15×10 moⅣL vs 1．27x10‘4 moⅣL)remained unchanged．The inhibition of， by WIN55212．2 was reversed by AM28 1，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 lAav by WIN55212·2．These results suggest that the inhibitory effect of cannabinoids on lm is mediated via the CB 1 receptors，that lead to inhibition of the AC·cAMP-PKA signaling pathway