Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions
Autor: | Hatsumi Yoshiki, Takanobu Taniguchi, Ikunobu Muramatsu, Matomo Nishio, Junsuke Uwada, Kiyonao Sada, Takayoshi Masuoka |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Isoflurophate Carbachol Colon Pharmacology Kidney Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Acetylcholine transport medicine Animals Choline Rats Wistar Acetylcholine receptor Cerebral Cortex Organic cation transport proteins Tetraethylammonium Dose-Response Relationship Drug biology Brain Biological Transport Heart Acetylcholine Rats 030104 developmental biology chemistry biology.protein Cholinergic Cholinesterase Inhibitors Esterase inhibitor 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Journal of Neurochemistry. 139:566-575 |
ISSN: | 0022-3042 |
Popis: | Functional acetylcholine receptors (AChRs) were recently demonstrated to exist not only in the plasma membrane but also intracellularly in brain tissues. In order to activate intracellular AChRs, endogenous hydrophilic ACh must cross the plasma membrane. Here, we examined the pharmacological characteristics of this process, including whether it is mediated by active ACh uptake. When ACh esterase (AChE) was suppressed by diisopropylfluorophosphate, [3 H]ACh was effectively taken up into segments of rat cerebral cortex and other brain regions, in contrast to peripheral tissues such as liver and kidney. The uptake of [3 H]ACh in rat cerebral cortex was temperature-dependent, and the uptake capacity was comparable to that of [3 H]choline. However, [3 H]ACh uptake was inhibited by lower concentrations of ACh, carbachol, tetraethylammonium (TEA), compared with uptake of [3 H]choline. Uptake of [3 H]ACh was also inhibited by several organic cations, including choline, hemicholinium-3 (HC-3), quinidine, decynium 22, clonidine, diphenhydramine, but was little affected by some amino acids and biogenic amines, corticosterone, spermine, atropine, and tetrodotoxin. Unlike diisopropylfluorophosphate, several ACh esterase inhibitors, including drugs for Alzheimer's disease, such as donepezil, galantamine, and rivastigmine, also suppressed the uptake of [3 H]ACh, but not [3 H]choline. These results indicate that in the brain, ACh is specifically taken up through a unique transport system with different pharmacological properties from known organic cation transporters (OCTs), and suggest that this mechanism may be involved in intracellular cholinergic transmission in the brain. |
Databáze: | OpenAIRE |
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