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Cannabinoids inhibit ATP-activated currents in rat trigeminal ganglionic neuroas
Pages: 745-752
Year: Issue:  6

Keyword:  cannabinoid receptor 1WIN55212-2P2X receptortrigeminal ganglionpatch-clamp technique;
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 1x10-13,1x10-12,1x10-11,1x10-10,1×10-9 and 1x10-8mol/L reduced IATP(induced by 1x10-4mol/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 WIN55212-2showed 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(1.15x10-4 mol/L vs 1.27x10-4 mol/L)remained unchanged.The inhibition of IATP by WIN55212-2 was reversed by AM281,suggesting that the inhibition was mediated via the CB1 receptor.Pretreatment with forskolin [an agonist of adenylyl cyclase (AC)] or 8-Br-cAMP reversed the inhibition of IATP by WIN55212-2.These results suggest that the inhibitory effect of cannabinoids on IATP is mediated via the CB1 receptors,that lead to inhibition of the AC-cAMP-PKA signaling pathway.
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