Neurochemical Research

, Volume 25, Issue 2, pp 303–312 | Cite as

Amyloid Beta Peptide Impaired Carbachol but not Glutamate-Mediated Phosphoinositide Pathways in Cultured Rat Cortical Neurons

  • Hsueh-Meei Huang
  • Hsio-Chung Ou
  • Shon-Jean Hsieh


Signal transduction systems, including cholinergic pathways, which are likely to be of pathophysiological significance are altered in Alzheimer's disease (AD). Muscarinic cholinergic receptors are linked to the hydrolysis of phosphoinositide, involving the production of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] and the mobilization of cytosolic free calcium concentrations ([Ca2+]i). Effects of amyloid peptide (Aβ) on these signals prior to neuronal degeneration were examined in cultured rat cortical cells. Aβ increased the release of lactate dehydrogenase (LDH) in a concentration-dependent manner, however, it was blocked by B27 supplement. Prolonged exposure to a sublethal dose of Aβ 25–35 or 1–42 disrupted carbachol-mediated release of Ins(1,4,5)P3 and [Ca2+]i, which was inhibited in media supplemented with B27 or the antioxidant vitamin E. In order to determine the specificity of the effect of Aβ, various agonists glutamate or KCl but not bradykinin which utilize the phosphoinositide cascade were investigated. Our results indicated that Aβ did not affect the stimulation of glutamate or KCl-mediated production of Ins(1,4,5)P3 or cause elevation in [Ca2+]i. Furthermore, metabotropic agonist trans-1-amino-cyclopentane-1,3,-dicarboxylate (ACPD) elevated calcium level was not inhibited by Aβ pretreatment. Taken together, the results demonstrate that a sublethal dose of Aβ selectively impaired cholinergic receptor-mediated signal transduction pathways, and antioxidant or B27 supplement attenuated this effect of Aβ. Alterations of cholinergic signaling by prolonged exposure to Aβ could be involved in cortical neurodegeneration that occurs in AD. Because functional loss of cholinergic pathways is an important aspect of AD, the differences in susceptibility of these two types of receptors prior to other signs of Aβ action is important and requires further investigation.

Amyloid peptide antioxidants trans-ACPD carbachol cytosolic free calcium concentration Ins(1,4,5)P3 cortical neuronal culture B27 supplement neurodegeneration 


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Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Hsueh-Meei Huang
    • 1
  • Hsio-Chung Ou
    • 2
  • Shon-Jean Hsieh
    • 2
  1. 1.Department of Education and Medical ResearchTaichung Veterans General HospitalTaichungTaiwan, R.O.C.
  2. 2.Department of Education and Medical ResearchTaichung Veterans General HospitalTaichungTaiwan, R.O.C.

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