1. Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones.
- Author
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Li, Zhi-Wang, Zhang, Jian, Ouyang, Chang-han, Li, Chao-Ying, Zhao, Feng-Bo, Liu, Yu-Wei, Ai, Yong-Xun, and Hu, Wang-Ping
- Subjects
GABA ,DRUG synergism ,TRIGEMINAL nerve ,CANNABINOIDS ,BIOSYNTHESIS ,LOCUS (Genetics) ,TARGETED drug delivery ,DRUG receptors ,SENSORY neurons ,LABORATORY rats ,ANALGESICS ,ANIMAL experimentation ,CELL receptors ,CYTOLOGICAL techniques ,DOSE-effect relationship in pharmacology ,SENSORY ganglia ,HETEROCYCLIC compounds ,HYDROCARBONS ,PIPERIDINE ,RATS ,SENSORY receptors ,TRANSFERASES ,PHARMACODYNAMICS - 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. [ABSTRACT FROM AUTHOR]- Published
- 2009
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