A NEUROCHEMICAL APPROACH FOR STUDYING RESPONSE TO ACETYLCHOLINE IN ALZHEIMERS-DISEASE

被引:13
作者
ALDER, JT [1 ]
CHESSELL, IP [1 ]
BOWEN, DM [1 ]
机构
[1] INST NEUROL,MIRIAM MARKS DEPT NEUROCHEM,LONDON WC1N 1PJ,ENGLAND
关键词
ALZHEIMERS DISEASE; ACETYLCHOLINE; MUSCARINIC; PHOSPHOLIPASE C; THERAPY;
D O I
10.1007/BF00969687
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proposal of cholinomimetic treatment as a rational basis for the therapy of Alzheimer's disease has been prematurely dismissed by some workers on the hypothesis of impaired coupling/signal transduction of postsynaptic cholinergic receptors. Disparity of reports studying such impairment may be due to inappropriate extrapolation of experimental systems to the physiological situation, as well as inadequate consideration of disease epiphenoma. In the present study we have used samples with short duration of terminal coma, collected using techniques to minimise postmortem autolysis, and samples obtained during neurosurgery to examine carbachol stimulated hydrolysis of [H-3]phosphatidylinositol (PI) as a marker for receptor/signal transduction integrity. The influence of postmortem delay was also studied using another series of samples and a rat model. While a significant correlation of postmortem delay and carbachol stimulated [3H]PI hydrolysis was found, comparison of pooled neurosurgical and postmortem controls with AD samples revealed no significant reduction. Thus this study concurs with a similar one previously reported here, using [3H]phosphatidylinositol 4,5-bisphosphate (1). They provide evidence for competent receptor-signal transduction events in AD, supporting the use of cholinomimetic therapy for disease treatment.
引用
收藏
页码:769 / 771
页数:3
相关论文
共 16 条
[1]   TETRAHYDROAMINOACRIDINE AND ALZHEIMERS-DISEASE [J].
BYRNE, EJ ;
ARIE, T .
BRITISH MEDICAL JOURNAL, 1994, 308 (6933) :868-869
[2]   LOCALIZATION OF MUSCARINIC (M(1)) AND OTHER NEUROTRANSMITTER RECEPTORS ON CORTICOFUGAL-PROJECTING PYRAMIDAL NEURONS [J].
CHESSELL, IP ;
FRANCIS, PT ;
PANGALOS, MN ;
PEARSON, RCA ;
BOWEN, DM .
BRAIN RESEARCH, 1993, 632 (1-2) :86-94
[3]  
CLARO E, 1989, J BIOL CHEM, V264, P18288
[4]   LOSS OF HIGH-AFFINITY AGONIST BINDING TO M1 MUSCARINIC RECEPTORS IN ALZHEIMERS-DISEASE - IMPLICATIONS FOR THE FAILURE OF CHOLINERGIC REPLACEMENT THERAPIES [J].
FLYNN, DD ;
WEINSTEIN, DA ;
MASH, DC .
ANNALS OF NEUROLOGY, 1991, 29 (03) :256-262
[5]   EFFECT OF CENTRAL CHOLINERGIC STIMULATION ON REGIONAL CEREBRAL BLOOD-FLOW IN ALZHEIMER-DISEASE [J].
GEANEY, DP ;
SOPER, N ;
SHEPSTONE, BJ ;
COWEN, PJ .
LANCET, 1990, 335 (8704) :1484-1487
[6]   INTRAVENOUS PHYSOSTIGMINE TREATMENT OF ALZHEIMERS-DISEASE EVALUATED BY PSYCHOMETRIC TESTING, REGIONAL CEREBRAL BLOOD-FLOW (RCBF) MEASUREMENT, AND EEG [J].
GUSTAFSON, L ;
EDVINSSON, L ;
DAHLGREN, N ;
HAGBERG, B ;
RISBERG, J ;
ROSEN, I ;
FERNO, H .
PSYCHOPHARMACOLOGY, 1987, 93 (01) :31-35
[7]   CEREBRAL PHARMACODYNAMICS OF PHYSOSTIGMINE IN ALZHEIMERS-DISEASE INVESTIGATED USING SINGLE-PHOTON COMPUTERIZED-TOMOGRAPHY [J].
HUNTER, R ;
WYPER, DJ ;
PATTERSON, J ;
HANSEN, MT ;
GOODWIN, GM .
BRITISH JOURNAL OF PSYCHIATRY, 1991, 158 :351-357
[8]   IMPAIRED PHOSPHOINOSITIDE HYDROLYSIS IN ALZHEIMERS-DISEASE BRAIN [J].
JOPE, RS ;
SONG, L ;
LI, XH ;
POWERS, R .
NEUROBIOLOGY OF AGING, 1994, 15 (02) :221-226
[9]  
JOPE RS, 1994, J NEUROCHEM, V62, P1
[10]   ORAL TETRAHYDROAMINOACRIDINE TREATMENT OF ALZHEIMERS-DISEASE EVALUATED CLINICALLY AND BY REGIONAL CEREBRAL BLOOD-FLOW AND EEG [J].
MINTHON, L ;
GUSTAFSON, L ;
DALFELT, G ;
HAGBERG, B ;
NILSSON, K ;
RISBERG, J ;
ROSEN, I ;
SEIVING, B ;
WENDT, PE .
DEMENTIA, 1993, 4 (01) :32-42