Modulation of glycine receptor function by the synthetic cannabinoid HU210.
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 (EC(50): 5.1 +/- 2.6 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50): 188.7 +/- 46.2 micromol/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.
Demir
Reyhan
R
Clinic for Anaesthesia and Critical Care Medicine, Hannover Medical School, Hannover, Germany.
Leuwer
Martin
M
de la Roche
Jeanne
J
Krampfl
Klaus
K
Foadi
Nilufar
N
Karst
Matthias
M
Dengler
Reinhard
R
Haeseler
Gertrud
G
Ahrens
Jörg
J
D000494:Allosteric Regulation / Q000187:drug effects*; D002461:Cell Line, Transformed; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005998:Glycine / Q000008:administration & dosage; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D018009:Receptors, Glycine / Q000819:agonists*; D014162:Transfection
D018009:Receptors, Glycine; D013759:Dronabinol; C062018:HU 211; D005998:Glycine