1. N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside induces sedative and hypnotic effects via GAD enzyme activation in mice
- Author
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Ruixia Kang, Jiangong Shi, Li-Na Tang, Yuankai Shi, J.W. Dong, and Jianjun Zhang
- Subjects
Agonist ,Male ,Adenosine ,medicine.drug_class ,Clinical Biochemistry ,Hypothalamus ,Glutamic Acid ,Pharmacology ,Toxicology ,Biochemistry ,Non-rapid eye movement sleep ,Behavioral Neuroscience ,chemistry.chemical_compound ,Mice ,Neurochemical ,medicine ,Animals ,Hypnotics and Sedatives ,Biological Psychiatry ,gamma-Aminobutyric Acid ,Cerebral Cortex ,biology ,Chemistry ,Glutamate Decarboxylase ,Electroencephalography ,Riboside ,Enzyme assay ,Semicarbazides ,Enzyme Activation ,Enzyme inhibitor ,Sedative ,4-Aminobutyrate Transaminase ,biology.protein ,GABAergic ,Sleep Stages - Abstract
Background and purpose N 6 -(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is an analog of N 6 -(4-hydroxybenzyl) adenine riboside (NHBA), which was originally isolated from Gastrodia elata Blume. Our laboratory has previously demonstrated that B2 can produce strong sedative and hypnotic effects, but the mechanism remains to be determined. There is evidence that gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the brain, plays a major role in sleep regulation, and participates in the sedative and hypnotic effects of B2. Therefore, we studied the interactions between B2 and several GABAergic neurochemical parameters based on the sedative and hypnotic effects of B2. Experimental approach The GABA and glutamic acid (Glu) in the mouse brain were derivatized with o-phthalaldehyde (OPA) and measured by high performance liquid chromatography–electrochemical detection (HPLC–ECD). The GAD and GABA-T enzyme activities were determined by measuring GABA and NADH production, respectively. The sleep structure analyses were performed by EEG studies in mice. Key results B2 increased the GABA levels and GAD enzyme activity in the mouse hypothalamus and cortex. The EEG results confirmed that B2 significantly shortened the sleep latency and increased the amount of NREM sleep. The GAD enzyme inhibitor semicarbazide (SCZ) blocked the sedative and hypnotic effects of B2. Conclusions and implications These findings suggest that the GAD enzyme plays a significant role in the sedative and hypnotic effects of B2. Therefore B2 may be a promising candidate for further clinical studies and the appropriate use of GAD agonist may be a promising approach for sleep disorders.
- Published
- 2014