Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons

Kume, Toshiaki; Sugimoto, Mitsuhiro; Takada, Youichiro; Yamaguchi, Toshiaki; Yonezawa, Atsushi; Katsuki, Hiroshi; Sugimoto, Hachiro; Akaike, Akinori

doi:10.1016/j.ejphar.2005.10.028

Cited by 58 publications

(52 citation statements)

References 35 publications

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“…Treatment with donepezil, galantamine or tacrine (0.1-10 mM) did not significantly upregulate a4-and a7-nAChR after 24-h treatment. 59) Thus, the neuroprotective action observed with acetylcholinesterase inhibitor treatment (10 mM, 24 h) in previous studies does not involve nAChR up-regulation; however, we observed significant up-regulation of a4-and a7-nAChR protein levels with longer treatment, after 4 days' chronic treatment with donepezil. 59,60) We also observed a significant increase in the proportion of neurons expressing a4-and a7-nAChR after chronic treatment with donepezil and galantamine.…”

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhcontrasting

confidence: 43%

“…59) Thus, the neuroprotective action observed with acetylcholinesterase inhibitor treatment (10 mM, 24 h) in previous studies does not involve nAChR up-regulation; however, we observed significant up-regulation of a4-and a7-nAChR protein levels with longer treatment, after 4 days' chronic treatment with donepezil. 59,60) We also observed a significant increase in the proportion of neurons expressing a4-and a7-nAChR after chronic treatment with donepezil and galantamine. These results are in good accordance with an in vivo study which showed that chronic administration of donepezil and galantamine at dose levels analogous to those used to treat patients with Alzheimer's disease significantly increased nAChR density in the frontal cortex and hippocampus of aged rats.…”

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhcontrasting

confidence: 43%

“…Although galantamine treatment increases the proportion of cells expressing a4-and a7-nAChR, we did not observe a significant increase in the a4-nAChR protein level in neurons treated with galantamine and only a modest increase in the level of a7-nAChR. 59) These results are supported by in vivo and in vitro studies which demonstrated that treatment with donepezil induced a significantly greater increase of nAChR density than treatment with galantamine in the frontal cortex of aged rats 55) and M10 cells stably expressing a4-nAChR.…”

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhmentioning

confidence: 63%

“…62,63) In treatment with acetylcholinesterase inhibitors, prolonged treatment with donepezil, galantamine and tacrine (1-10 mM) significantly potentiated the nicotine-induced increase in intracellular calcium concentration ([Ca 2ϩ ] i ), suggesting that chronic acetylcholinesterase inhibitor treatment does not desensitize nAChR. 59) These results are interesting given that chronic administration of donepezil and galantamine extends the decay time of long-term potentiation (LTP) which, in the same study, was demonstrated to be significantly correlated to cognitive function. 55) It was suggested that the increased density of functional nAChR enhances LTP, but the functional state of nAChR was not examined in the previous study.…”

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhmentioning

confidence: 99%

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Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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Protection of neurons from neuronal damage and cell death in neurodegenerative disease is a major challenge in neuroscience research. Donepezil, galantamine and tacrine are acetylcholinesterase inhibitors used for the treatment of Alzheimer's disease, and were believed to be symptomatic drugs whose therapeutic effects are achieved by slowing the hydrolysis of acetylcholine at synaptic termini. However, recent accumulated evidence strongly suggests that these acetylcholinesterase inhibitors also possess neuroprotective properties whose mechanism is independent of acetylcholinesterase inhibition. We have shown that acetylcholinesterase inhibitors protect neurons from glutamate-induced neurotoxicity in the primary culture of rat cortical neurons. It was also found that acetylcholinesterase inhibitor treatment induces up-regulation of nicotinic receptor expression levels, a property which may also have some bearing on their therapeutic effects. We next showed that a a4 and a a7-nicotinic receptors play important roles in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation. Our results also demonstrate the important roles of the phosphatidylinositol 3-kinase pathway downstream of nicotinic receptors in protecting neurons from death and up-regulating nicotinic receptors. This review summarizes recent findings on the roles of the nicotinic receptor in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation.

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Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhcontrasting

confidence: 43%

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhcontrasting

confidence: 43%

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhmentioning

confidence: 63%

Section: Nicotinic Receptor Up-regulation By Acetylcholinesterase Inhmentioning

confidence: 99%

See 2 more Smart Citations

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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“…It has been reported that galantamine (10 mM, 4 days) dose not significantly affect the mRNA level and protein expression of nAChR subunits (Kume et al, 2005). Galantamine increases cholinergic function mainly in two ways: (a) increasing the concentration of acetylcholine through a competitive reversible inhibition of acetylcholine hydrolysis by acetylcholinesterase, which will increase the extracellular acetylcholine concentration and (b) allosteric modulation of nAChRs (Woodruff-Pak and Santos, 2000).…”

Section: Discussionmentioning

confidence: 98%

The Allosteric Potentiation of Nicotinic Acetylcholine Receptors by Galantamine Ameliorates the Cognitive Dysfunction in Beta Amyloid25–35 I.c.v.-Injected Mice: Involvement of Dopaminergic Systems

Wang

Noda

Zhou

et al. 2006

Neuropsychopharmacol

125

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Galantamine, a drug for Alzheimer's disease, is a novel cholinergic agent with a dual mode of action, which inhibits acetylcholinesterase and allosterically modulates nicotinic acetylcholine receptors (nAChRs), as a result stimulates catecholamine neurotransmission. In the present study, we investigated whether galantamine exerts cognitive improving effects through the allosteric modulation of nAChR in the intracerebroventricular beta amyloid (Ab) 25À35 -injected animal model of Alzheimer's disease. Galantamine (3 mg/kg p.o.) significantly increased the extracellular dopamine release in the hippocampus of saline-and Ab 25À35 -injected mice. The effects of nicotine on the extracellular dopamine release were potentiated by galantamine, but antagonized by mecamylamine, a nAChR antagonist. Ab 25À35 -injected mice, compared with saline-injected mice, could not discriminate between new and familiar objects in the novel object recognition test and exhibited less freezing response in the fear-conditioning tasks, suggesting Ab 25À35 induced cognitive impairment. Galantamine improved the Ab 25À35 -induced cognitive impairment in the novel object recognition and fear-conditioning tasks. These improving effects of galantamine were blocked by the treatment with mecamylamine, SCH-23390, a dopamine-D1 receptor antagonist, and sulpiride, a dopamine-D2 receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist. This study provides the first in vivo evidence that galantamine augments dopaminergic neurotransmission within the hippocampus through the allosteric potentiation of nAChRs. The improving-effects of galantamine on the Ab 25À35 -induced cognitive impairment may be mediated through the activation of, at least in part, dopaminergic systems, and the enhancement of dopamine release may be one of multiple mechanisms underlying the therapeutic benefit of galantamine.

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Structural Features and Hydrogen‐Bond Properties of Galanthamine and Codeine: An Experimental and Theoretical Study

Atkinson

Baguet

Galland

et al. 2011

Chemistry A European J

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Structural features of galanthamine and codeine, two allosteric potentiating ligands of nicotinic acetylcholine receptors (nAChRs), have been investigated through experimental studies in solution by FTIR and NMR spectroscopy and by quantum chemical calculations in the isolated state. The infrared spectra accumulated in solvents of various polarities show that the intramolecular OH···O hydrogen bond in galanthamine is stronger than the corresponding interaction in codeine. Molecular electrostatic potential calculations allow rationalisation of the experimental trends. NOE measurements on the two ligands in the same solvent range show significant differences. In apolar solvents, the NMR spectroscopic data indicate the occurrence of CH···O hydrogen-bond interactions, whereas in the more polar solvents, a trans orientation of the methoxy group with respect to the furanyl oxygen atom is favoured. A natural bond orbital (NBO) analysis provides evidence that these stabilising interactions originate in the hyperconjugation between the lone pairs of the furanyl oxygen atoms, n(O), and the methoxy antibonding σ*(C-H) orbitals within the two molecules. Despite the strong structural similarities between the two allosteric modulators, FTIR equilibrium constants measurements of hydrogen-bond complexation combined with quantum chemistry calculations point out the significant increase of hydrogen-bond accepting strength of galanthamine relative to codeine. This increase is mainly assignable to the stronger hydrogen-bond basicity of the hydroxyl group, and to a lesser extent to the higher hydrogen-bond accepting strength of the amino nitrogen of galanthamine in comparison with the corresponding groups of codeine. An analysis of the interactions that occur between the two ligands and acetylcholine esterase (AChE) suggests significant differences with Trp84, a key component of the AChE catalytic active site. In contrast, both ligands appear to interact similarly with acetylcholine binding protein (AChBP).

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Up-regulation of nicotinic acetylcholine receptors by central-type acetylcholinesterase inhibitors in rat cortical neurons

Cited by 58 publications

References 35 publications

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

The Allosteric Potentiation of Nicotinic Acetylcholine Receptors by Galantamine Ameliorates the Cognitive Dysfunction in Beta Amyloid25–35 I.c.v.-Injected Mice: Involvement of Dopaminergic Systems

Structural Features and Hydrogen‐Bond Properties of Galanthamine and Codeine: An Experimental and Theoretical Study

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