Effects of the M1 agonist xanomeline on processing of human β-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells

被引：27

作者：

DeLapp, N ^{[1
]}

Wu, S

Belagaje, R

Johnstone, E

Little, S

Shannon, H

Bymaster, F

Calligaro, D

Mitch, C

Whitesitt, C

Ward, J

Sheardown, M

Fink-Jensen, A

Jeppesen, L

Thomsen, C

Sauerberg, P

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

[2] Novo Nordisk AS, CNS Div, Malov, Denmark

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1998年 / 244卷 / 01期

关键词：

D O I：

10.1006/bbrc.1998.8235

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：

Complimentary DNA (cDNA) encoding human beta-amyloid precursor protein familial Alzheimer's disease (FAD) Swedish mutant (beta APP(SM)) form was cloned into a mammalian expression vector (PK255) containing the CMV promoter. The vector was transfected into Chinese hamster ovary cells containing human muscarinic m1 receptors (CHO-m1), and clonal cells stably expressing beta APP(SM) were isolated, The effects of m1-receptor activation by the selective m1 agonist xanomeline and the non-selective muscarinic agonist carbachol on processing of beta APP(SM) to release soluble APP (APPs) and beta-amyloid peptide (A beta) were compared. Xanomeline stimulated APP release with a potency 1000-fold greater than that observed for carbachol. Concentrations of carbachol and xanomeline producing maximal effects on APPs release reduced the secretion of A beta by 28 and 46%, respectively. These results extend previous studies with xanomeline and suggest that cholinergic replacement therapy for Alzheimer's disease may reduce amyloid deposition. (C) 1998 Academic Press.

引用

页码：156 / 160

页数：5

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