HIGH-AFFINITY HIPPOCAMPAL [H-3] GLIBENCLAMIDE BINDING-SITES ARE PRESERVED IN ALZHEIMERS-DISEASE

被引:6
作者
IKEDA, M
DEWAR, D
MCCULLOCH, J
机构
[1] UNIV GLASGOW,WELLCOME SURG INST,WELLCOME NEUROSCI GRP,GARSCUBE ESTATE,GLASGOW G61 1QH,SCOTLAND
[2] UNIV GLASGOW,HUGH FRASER NEUROSCI LABS,GLASGOW G61 1QH,SCOTLAND
基金
英国惠康基金;
关键词
ALZHEIMERS DISEASE; K+ CHANNELS; GLIBENCLAMIDE; HIPPOCAMPUS;
D O I
10.1007/BF02257672
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
ATP-sensitive K+ channels were examined in sections of the hippocampus from patients with Alzheimer's disease and age-matched control subjects by means of quantitative autoradiography. ATP-sensitive K+ channels were labelled with the sulfonylurea, [H-3]-glibenclamide, which is a potent blocker of these channels. The density of cells in the subiculum and the activity of choline acetyltransferase were determined in the same hippocampal tissue samples. In the hippocampal formation of control subjects, the density of high affinity [H-3]-glibenclamide binding sites ranged from 17.6 +/- 0.9 pmoles/g in the presubiculum to 11.6 +/- 0.6 pmoles/g in the parvopyramidal layer of the presubiculum. There was no difference between Alzheimer patients and controls in the level of high affinity [H-3]-glibenclamide binding in any hippocampal region although there was a marked loss of subicular cells (reduced by 29% compared to controls) and a reduction in choline acetyltransferase activity (reduced by 60% compared to controls). The results suggest that ATP-sensitive K+ channels are associated with elements in the hippocampus which are preserved in Alzheimer's disease.
引用
收藏
页码:177 / 184
页数:8
相关论文
共 27 条
[1]   POTASSIUM CHANNEL ACTIVATORS ABOLISH EXCITOTOXICITY IN CULTURED HIPPOCAMPAL PYRAMIDAL NEURONS [J].
ABELE, AE ;
MILLER, RJ .
NEUROSCIENCE LETTERS, 1990, 115 (2-3) :195-200
[2]  
Amaral DG, 1990, HUMAN NERVOUS SYSTEM, P711
[3]   GLUCOSE, SULFONYLUREAS, AND NEUROTRANSMITTER RELEASE - ROLE OF ATP-SENSITIVE K+ CHANNELS [J].
AMOROSO, S ;
SCHMIDANTOMARCHI, H ;
FOSSET, M ;
LAZDUNSKI, M .
SCIENCE, 1990, 247 (4944) :852-854
[4]   ADENOSINE-5'-TRIPHOSPHATE-SENSITIVE ION CHANNELS IN NEONATAL RAT CULTURED CENTRAL NEURONS [J].
ASHFORD, MLJ ;
STURGESS, NC ;
TROUT, NJ ;
GARDNER, NJ ;
HALES, CN .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1988, 412 (03) :297-304
[5]   GALANIN AND GLIBENCLAMIDE MODULATE THE ANOXIC RELEASE OF GLUTAMATE IN RAT CA3 HIPPOCAMPAL-NEURONS [J].
BENARI, Y .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1990, 2 (01) :62-68
[6]   ACTIVATORS OF ATP-SENSITIVE K+ CHANNELS REDUCE ANOXIC DEPOLARIZATION IN CA3 HIPPOCAMPAL-NEURONS [J].
BENARI, Y ;
KRNJEVIC, K ;
CREPEL, V .
NEUROSCIENCE, 1990, 37 (01) :55-60
[7]   CHARACTERIZATION, PURIFICATION, AND AFFINITY LABELING OF THE BRAIN [H-3] GLIBENCLAMIDE-BINDING PROTEIN, A PUTATIVE NEURONAL ATP-REGULATED K+ CHANNEL [J].
BERNARDI, H ;
FOSSET, M ;
LAZDUNSKI, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (24) :9816-9820
[8]   RAPID RADIOCHEMICAL METHOD FOR DETERMINATION OF CHOLINE-ACETYLTRANSFERASE [J].
FONNUM, F .
JOURNAL OF NEUROCHEMISTRY, 1975, 24 (02) :407-409
[9]  
GEHLERT DR, 1991, J PHARMACOL EXP THER, V257, P901
[10]   EXCITATORY AMINO-ACIDS AND ALZHEIMERS-DISEASE [J].
GREENAMYRE, JT ;
YOUNG, AB .
NEUROBIOLOGY OF AGING, 1989, 10 (05) :593-602