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Pharmacological evidence of specific acetylcholine transport in rat cerebral cortex and other brain regions
Author(s) -
Muramatsu Ikunobu,
Yoshiki Hatsumi,
Uwada Junsuke,
Masuoka Takayoshi,
Sada Kiyonao,
Taniguchi Takanobu,
Nishio Matomo
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13843
Subject(s) - acetylcholine , chemistry , choline , cholinergic , tetraethylammonium , muscarinic acetylcholine receptor , organic cation transport proteins , medicine , pharmacology , endocrinology , biochemistry , biology , receptor , transporter , potassium , organic chemistry , gene
Functional acetylcholine receptors ( AC hRs) were recently demonstrated to exist not only in the plasma membrane but also intracellularly in brain tissues. In order to activate intracellular AC hRs, endogenous hydrophilic AC h must cross the plasma membrane. Here, we examined the pharmacological characteristics of this process, including whether it is mediated by active AC h uptake. When AC h esterase ( AC hE) was suppressed by diisopropylfluorophosphate, [ 3 H] AC h 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] AC h in rat cerebral cortex was temperature‐dependent, and the uptake capacity was comparable to that of [ 3 H]choline. However, [ 3 H] AC h uptake was inhibited by lower concentrations of AC h, carbachol, tetraethylammonium ( TEA ), compared with uptake of [ 3 H]choline. Uptake of [ 3 H] AC h 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 AC h esterase inhibitors, including drugs for Alzheimer's disease, such as donepezil, galantamine, and rivastigmine, also suppressed the uptake of [ 3 H] AC h, but not [ 3 H]choline. These results indicate that in the brain, AC h is specifically taken up through a unique transport system with different pharmacological properties from known organic cation transporters ( OCT s), and suggest that this mechanism may be involved in intracellular cholinergic transmission in the brain.