title: Endocannabinoid 2-Arachidonoylglycerol Suppresses LPS-Induced Inhibition of A-Type Potassium Channel Currents in Caudate Nucleus Neurons Through CB1 Receptor.
abstract: Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from some proinflammatory stimuli. However, the neuroprotective mechanism of 2-AG is complex and has not been fully understood. A-type K(+) channels critically regulate neuronal excitability and have been demonstrated to be associated with some nervous system diseases. The aim of this study was to explore whether A-type K(+) channels were involved in neurotoxicity of lipopolysaccharides (LPS) and the neuroprotective mechanism of 2-AG in CN neurons. Whole cell patch clamp recording was used to investigate the influence of LPS on the function of A-type K(+) channels and its modulation by 2-AG in primary cultured rat CN neurons. Our findings showed that in cultured CN neurons, LPS significantly decreased the A-type potassium currents (I A) in a voltage-insensitive way. The further data demonstrated that an elevation of 2-AG levels by directly applying exogenous 2-AG or inhibiting monoacylglycerol lipase (MAGL) to prevent 2-AG hydrolysis was capable of suppressing the LPS-induced inhibition of IA and the action of 2-AG is mediated through CB1 receptor-dependant way. The study provides a better understanding of inflammation-related neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People's Republic of China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People's Republic of China.|Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, Hubei, People's Republic of China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurology, The First Hospital of Yichang, Institute of Translational Neuroscience, Three Gorges University College of Medicine, 443000, Yichang, Hubei, People's Republic of China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Zha
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People's Republic of China. yhw0224@yahoo.com.|Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, Hubei, People's Republic of China. yhw0224@yahoo.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yang
mesh_terms: D000200:Action Potentials; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008994:Monoacylglycerol Lipases / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D008070:Lipopolysaccharides; D024642:Potassium Channels, Voltage-Gated; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate; D008994:Monoacylglycerol Lipases
keywords: 2-Arachidonoylglycerol (2-AG); A-type potassium channel; Cannabinoid receptor; Caudate nucleus (CN); Lipopolysaccharide (LPS); Monoacylglycerol lipase (MAGL)