Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?
- 35 Downloads
In the presence of 9-amino-1, 2, 3,4-tetrahydroacridine (THA) 10−4M or physostigmine 10−4 M, the in vitro3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10−4 M and physostigmine 10−4 M significantly increased the release of3H-ACh in AD/SDAT brain tissue. This facilitating effect on3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10−6 M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10−5 M significantly increased the3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with3H-nicotine,3H-ACh and3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.
Key wordsAlzheimer's disease 3H-Acetylcholine release THA physostigmine nicotinic receptors muscarinic receptors receptor subtypes
Unable to display preview. Download preview PDF.
- Adem A (1987) Characterization of muscarinic and nicotinic receptors in neural and non-neural tissue: Changes in Alzheimer's disease. Acta Universitas Upsaliensis 32: 4–61Google Scholar
- Corkin S (1981) Acetylcholine, aging and Alzheimer's disease. Trends Neuro Sci 12: 287–290Google Scholar
- Caulfield MP, Straughan DW, Cross AJ, Cron T, Birdsall NJM (1982) Cortical muscarinic receptor subtypes and Alzheimer's disease. Lancet 11: 1277Google Scholar
- Hardy JA, Adolfsson R, Alafuzoff I, Bucht S, Marcusson J, Nyberg P, Perdahl E, Wester P, Winblad B (1985) Transmitter deficits in Alzheimer's disease. Neurochem Int 7: 545–563Google Scholar
- Heilbronn E (1961) Inhibition of cholinesterases by tetrahydroaminacrin. Acta Chem Scand 15: 1386–1390Google Scholar
- Mohs RC, Davies BM, Mathé AA, Rosen WG, Johns CA, Greenwald BS, Horvath TB, Davies KL (1985) Intravenous and oral physostigmine in Alzheimer's disease. Interdiscipl Top Gerontol 20: 140–152Google Scholar
- Nordberg A, Winblad B (1986a) Brain nicotinic and muscarinic receptors in normal aging and dementia. In: Fisher A, Hanin I, Lachman C (eds) Alzheimer's and Parkinson's disease: strategies in research and development. Plenum Press, New York, pp 95–108 (Advances in behavioral biology, vol 29)Google Scholar
- Nordberg A, Adem A, Nilsson L, Winblad B (1987a) Cholinergic deficits in CNS and peripheral non-neyrolan tissue in Alzheimer dementia. In: Dowdall M, Hawthorne J (eds) Cellular and molecular basis of cholinergic function. Ellis Horwood, Chichester, Sussex, pp 858–868Google Scholar
- Nordberg A, Adem A, Nilsson L, Winblad B (1987b) Nicotinic and muscarinic cholinergic receptor heterogeneity in human brain at normal aging and dementia of Alzheimer type. In: Pepeu G, Tomlinson B, Wischik CM (eds) Proc int symp “New trends in aging research”. Fidia Research series, Liviano Press (in press)Google Scholar
- Sims NR, Smith CCT, Davison AN, Bowen DM, Flack RHA, Snowden JS (1980) Glucose metabolism and acetylcholine synthesis in relation to neuronal activity in Alzheimer's disease. Lancet i: 333–336Google Scholar
- Szerb JC, Somogyi GT (1973) Depression of acetylcholine release from cortical slices by cholinesterase inhibition and by oxotremorine. Nature (New Biol) 241: 121–122Google Scholar