Cannabinoids inhibit ATP-activated currents in rat trigeminal ganglionic neurons.
- Author:
Jing-Jing SHEN
1
;
Chang-Jin LIU
;
Ai LI
;
Xin-Wu HU
;
Yong-Li LU
;
Lei CHEN
;
Ying ZHOU
;
Lie-Ju LIU
Author Information
1. Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
- Publication Type:Journal Article
- MeSH:
Adenosine Triphosphate;
physiology;
Animals;
Benzoxazines;
pharmacology;
Cannabinoids;
pharmacology;
Morpholines;
pharmacology;
Naphthalenes;
pharmacology;
Neurons;
drug effects;
physiology;
Patch-Clamp Techniques;
Pyrazoles;
pharmacology;
Rats;
Receptor, Cannabinoid, CB1;
agonists;
antagonists & inhibitors;
Signal Transduction;
Trigeminal Ganglion;
drug effects;
physiology
- From:
Acta Physiologica Sinica
2007;59(6):745-752
- CountryChina
- Language:English
-
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 (I(ATP)) 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) 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 CB1 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 CB1 receptors, that lead to inhibition of the AC-cAMP-PKA signaling pathway.
