INHIBITOR OF ANTAGONIST BINDING TO THE MUSCARINIC RECEPTOR IS ELEVATED IN ALZHEIMERS BRAIN

被引：13

作者：

FREY, WH ^{[1
]}

EMORY, CR ^{[1
]}

WIEBENGA, ME ^{[1
]}

SAXENA, S ^{[1
]}

CARDELLI, D ^{[1
]}

ALA, TA ^{[1
]}

TOLLEFSON, GD ^{[1
]}

机构：

[1] ST PAUL RAMSEY MED CTR,RAMSEY CLIN,ALZHEIMERS TREATMENT & RES CTR,DEPT NEUROL,ST PAUL,MN 55101

来源：

BRAIN RESEARCH | 1994年 / 655卷 / 1-2期

关键词：

ALZHEIMERS; MUSCARINIC RECEPTOR; ENDOGENOUS INHIBITOR; BRAIN;

D O I：

10.1016/0006-8993(94)91609-8

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The 100,000 x g supernatant fraction of human brain contains endogenous inhibitors of antagonist binding to the muscarinic receptor. Significantly greater inhibition was observed with Alzheimer's than non-demented control supernatant fractions. Low molecular weight inhibitor was separated from larger inhibitor species by membrane dialysis (3,500 dalton cut-off). The activity of low molecular weight inhibitor was greatly increased by sulfhydryl reducing agents. While the low molecular weight inhibitor was stable to heat, acid and base for short lime periods (< 20 min), it was inactivated by acid hydrolysis (50% loss after 16 h, 100% loss after 96 h). The low molecular weight inhibitor activity is elevated approximately three-fold in Alzheimer's brain. The low molecular weight inhibitor from Alzheimer's brain was found to be a non-competitive inhibitor. This is the first report of endogenous inhibitors in human brain of ligand binding to the muscarinic receptor and of increased inhibitor activity in Alzheimer's disease.

引用

页码：153 / 160

页数：8