Journal of the Neurological Sciences
Volume 223, Issue 2 , Pages 145-148, 30 August 2004

Decrease in GTP-sensitive high affinity agonist binding of muscarinic acetylcholine receptors in autopsied brains of dementia with Lewy bodies and Alzheimer's disease

  • Kazumasa Shiozaki

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +81-45-787-2667; fax: +81-45-783-2540.
    • Department of Psychiatry, Yokohama City University School of Medicine, 3–9 Fukuura, Kanazawa , Yokohama 236-0004, Japan
    • ,
  • Eizo Iseki

      Affiliations

    • Department of Psychiatry, Koto Geriatric Medical Center, Juntendo University School of Medicine, 3-3-20 Shinsuna, Koto, Tokyo 136-0075, Japan

Received 20 January 2004; received in revised form 5 May 2004; accepted 6 May 2004.

Abstract 

To determine changes in signal transduction from the muscarinic acetylcholine receptor (mAChR) to G protein in brain tissue of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we investigated GTP-sensitive agonist high affinity binding, which is considered an index of the formation of the mAChR-G protein complex. Brain tissue was obtained at necropsy from eight patients with DLB, nine patients with Alzheimer's disease and seven patients as controls. Membrane fractions were prepared from frontal and temporal cerebral tissues. Displacement curves of [3H]l-quinuclidinyl benzilate (QNB) binding by carbamylcholine were analyzed by the nonlinear least-squares methods. The proportion of and affinity for the agonist in GTP-sensitive agonist high affinity binding were estimated. The percentages GTP-sensitive agonist high affinity bindings were significantly decreased in DLB (P<0.01) and Alzheimer's disease (P<0.05) only in the frontal lobe. There were no significant differences in the temporal lobe. The ratio of agonist affinity (Kd value of low affinity component/Kd value of high affinity component) did not significantly differ among groups in either the frontal lobe or temporal lobe. The concentration of mAChR-G protein complex is considered reduced in the frontal lobe of brains with DLB and Alzheimer's disease. Therefore, signal transduction from mAChR to G protein was disturbed in the frontal lobe in these diseases.

Keywords:  Muscarinic acetylcholine receptor (mAChR), GTP-binding regulatory protein (G protein), GTP-sensitive agonist high affinity binding, mAChR-G protein complex, Dementia with Lewy bodies (DLB), Alzheimer's disease (AD)

Abbreviations:  mAChR, muscarinic acetylcholine receptor, G protein, GTP-binding regulatory protein, QNB, l-quinuclidinyl benzilate, GTPγS, guanosine 5′-O-(3-thiotriphosphate), EDTA, ethylenediaminetetraacetic acid

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PII: S0022-510X(04)00145-5

doi:10.1016/j.jns.2004.05.002

Journal of the Neurological Sciences
Volume 223, Issue 2 , Pages 145-148, 30 August 2004

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