Modulation of Glycine Receptor Function by the Synthetic Cannabinoid HU210

被引：21

作者：

Demir, Reyhan ^{[1
]}

Leuwer, Martin ^{[3
]}

de la Roche, Jeanne ^{[1
]}

Krampfl, Klaus ^{[2
]}

Foadi, Nilufar ^{[1
]}

Karst, Matthias ^{[1
]}

Dengler, Reinhard ^{[2
]}

Haeseler, Gertrud ^{[1
]}

Ahrens, Joerg ^{[1
]}

机构：

[1] Hannover Med Sch, Clin Anaesthesia & Crit Care Med, DE-30623 Hannover, Germany

[2] Hannover Med Sch, Dept Neurol & Neurophysiol, DE-30623 Hannover, Germany

[3] Univ Liverpool, Div Clin Sci, Liverpool L69 3BX, Merseyside, England

来源：

PHARMACOLOGY | 2009年 / 83卷 / 05期

关键词：

Glycine receptor; Inhibitory synaptic transmission; Anti-nociceptive; Cannabinoids; HU210; SUPERFICIAL DORSAL HORN; NEUROPATHIC PAIN; THERAPEUTIC TARGET; SPINAL-CORD; RAT; GABA(A); DELTA(9)-TETRAHYDROCANNABINOL; INHIBITION; MEMBRANE; SYNAPSES;

D O I：

10.1159/000209291

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. HU210 is a non-psychotropic, synthetic cannabinoid. As we hypothesized that non-CB receptor mechanisms of HU210 might contribute to its anti-inflammatory and anti-nociceptive effects we investigated the interaction of HU210 with strychnine-sensitive alpha(1) glycine receptors by using the whole-cell patch clamp technique. HU210 showed a positive allosteric modulating effect in a low micromolar concentration range (EC50 : 5.1 +/- 2.6 mu mol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 mu mol/l (EC50 : 188.7 +/- 46.2 mu mol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for HU210 mediating some of its anti-inflammatory and anti-nociceptive properties. Copyright (C) 2009 S. Karger AG, Basel

引用

页码：270 / 274

页数：5

共 33 条

[1] Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors [J].

Agarwal, Nitin ;

Pacher, Pal ;

Tegeder, Irmgard ;

Amaya, Fumimasa ;

Constantin, Cristina E. ;

Brenner, Gary J. ;

Rubino, Tiziana ;

Michalski, Christoph W. ;

Marsicano, Giovanni ;

Monory, Krisztina ;

Mackie, Ken ;

Marian, Claudiu ;

Batkai, Sandor ;

Parolaro, Daniela ;

Fischer, Michael J. ;

Reeh, Peter ;

Kunos, George ;

Kress, Michaela ;

Lutz, Beat ;

Woolf, Clifford J. ;

Kuner, Rohini .

NATURE NEUROSCIENCE, 2007, 10 (07) :870-879

[2] PGE2 selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons [J].

Ahmadi, S ;

Lippross, S ;

Neuhuber, WL ;

Zeilhofer, HU .

NATURE NEUROSCIENCE, 2002, 5 (01) :34-40

[3]

AHRENS J, 2008, NAUNYN SCHMIEDEBERGS

[4]

Ashton JC, 2007, CURR OPIN INVEST DR, V8, P373

[5] Glycine receptors: recent insights into their structural organization and functional diversity [J].

Betz, Heinrich ;

Laube, Bodo .

JOURNAL OF NEUROCHEMISTRY, 2006, 97 (06) :1600-1610

[6] Mechanisms of pain modulation in chronic syndromes [J].

Bolay, H ;

Moskowitz, MA .

NEUROLOGY, 2002, 59 (05) :S2-S7

[7] Targeting cannabinoid agonists for inflammatory and neuropathic pain [J].

Cheng, Yuan ;

Hitchcock, Stephen A. .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2007, 16 (07) :951-965

[8] On the pharmacological properties of Δ9-tetrahydrocannabinol (THC) [J].

Costa, Barbara .

CHEMISTRY & BIODIVERSITY, 2007, 4 (08) :1664-1677

[9] Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain [J].

Coull, JAM ;

Boudreau, D ;

Bachand, K ;

Prescott, SA ;

Nault, F ;

Sik, A ;

De Koninck, P ;

De Koninck, Y .

NATURE, 2003, 424 (6951) :938-942

[10] Antihyperalgesic properties of the cannabinoid CT-3 in chronic neuropathic and inflammatory pain states in the rat [J].

Dyson, A ;

Peacock, M ;

Chen, A ;

Courade, JP ;

Yaqoob, M ;

Groarke, A ;

Brain, C ;

Loong, Y ;

Fox, A .

PAIN, 2005, 116 (1-2) :129-137

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