[The synthetic cannabinoid analog WIN 55,212-2 potentiates the amplitudes of glycine-activated currents].
Most of the pharmacological actions of cannabinoids are mediated by CB1 receptors. There is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Our data demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. Here, we report that cannabinoid receptors agonist WIN 55,212-2, in a CB1 receptor independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I(Gly)) in acutely isolated hippocampal CA3 and CA1 pyramidal neurons. The maximal potentiation by this compound was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. Also WIN 55,212-2 significantly accelerated the desensitization of Gly-induced chloride current and significantly decreased the rise time. The effects of WIN 55,212-2 on I(Gly) were not attenuated in the presence of CB1 receptor antagonist AM251, suggesting that CB1 receptor activation are not involved in action of cannabinoid on GlyRs. Altogether these data allow us to suggest the existence of a CB1R independent action of cannabinoids directly on glycine-activated currents, representing a novel antinociceptive mechanism of this compounds.
Iatsenko
N M
NM
Tsintsadze
T Sh
TSh
Lozova
N O
NO
D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*
D048588:Benzoxazines; D002186:Cannabinoids; D002712:Chlorides; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018009:Receptors, Glycine; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D005998:Glycine