Potentiation by WIN 55,212-2 of GABA-activated Currents in Rat Trigeminal Ganglion Neurones

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2009 Nov 18

PMID 19917064

Citations 4

Authors

Zhi-Wang Li

Jian Zhang

Chang-han Ouyang

Chao-Ying Li

Feng-bo Zhao

Yu-Wei Liu

Yong-Xun Ai

Wang-Ping Hu

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Although both natural and synthetic cannabinoid compounds have been shown to exert an antinociceptive effect on acute and persistent pain, the anatomical locus of the target of cannabinoid-induced analgesia has not been fully elucidated. Here, we investigated the effects of the cannabinoid agonist WIN 55,212-2 on GABA-activated currents (I(GABA)) in rat primary sensory neurones.

Experimental Approach: In the present study, experiments were performed on neurones freshly isolated from rat trigeminal ganglion (TG) by using whole-cell patch clamp and repatch techniques.

Key Results: GABA-evoked inward currents were potentiated by pretreatment with WIN 55,212-2 in a concentration-dependent manner (10(-10)-10(-8) M). WIN 55,212-2 shifted the GABA concentration-response curve upwards, with an increase of 30.3 +/- 3.7% in the maximal current response but with no significant change in the EC(50) (agonist concentration producing a half-maximal response) value. WIN 55,212-2 potentiated the responses to GABA in a manner independent of holding potential and in the absence of any change in the reversal potential of the current. This potentiation of I(GABA) induced by WIN 55,212-2 was almost completely blocked by AM 251 (3 x 10(-8) M), a CB(1) receptor antagonist, and, using the repatch technique, was found to be abolished after intracellular dialysis with the protein kinase A (PKA) activator cAMP or the PKA inhibitor H89.

Conclusions And Implications: The potentiation by WIN 55,212-2 of I(GABA) in primary sensory neurones may help to elucidate the mechanism underlying the modulation of analgesia by cannabinoids in the spinal dorsal horn.

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