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Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones.
Br J Pharmacol 2009; 158(8):1904-10BJ

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.

Authors+Show Affiliations

Wuhan Institute of Neuroscience and Drug Research, Jianghan University, Wuhan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19917064

Citation

Li, Zhi-Wang, et al. "Potentiation By WIN 55,212-2 of GABA-activated Currents in Rat Trigeminal Ganglion Neurones." British Journal of Pharmacology, vol. 158, no. 8, 2009, pp. 1904-10.
Li ZW, Zhang J, Ouyang CH, et al. Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones. Br J Pharmacol. 2009;158(8):1904-10.
Li, Z. W., Zhang, J., Ouyang, C. H., Li, C. Y., Zhao, F. B., Liu, Y. W., ... Hu, W. P. (2009). Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones. British Journal of Pharmacology, 158(8), pp. 1904-10. doi:10.1111/j.1476-5381.2009.00482.x.
Li ZW, et al. Potentiation By WIN 55,212-2 of GABA-activated Currents in Rat Trigeminal Ganglion Neurones. Br J Pharmacol. 2009;158(8):1904-10. PubMed PMID: 19917064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation by WIN 55,212-2 of GABA-activated currents in rat trigeminal ganglion neurones. AU - Li,Zhi-Wang, AU - Zhang,Jian, AU - Ouyang,Chang-han, AU - Li,Chao-Ying, AU - Zhao,Feng-Bo, AU - Liu,Yu-Wei, AU - Ai,Yong-Xun, AU - Hu,Wang-Ping, PY - 2009/11/18/entrez PY - 2009/11/18/pubmed PY - 2010/3/13/medline SP - 1904 EP - 10 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 158 IS - 8 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/19917064/Potentiation_by_WIN_55212_2_of_GABA_activated_currents_in_rat_trigeminal_ganglion_neurones_ L2 - https://doi.org/10.1111/j.1476-5381.2009.00482.x DB - PRIME DP - Unbound Medicine ER -