Effects of the M1 agonist xanomeline on processing of human beta-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells.
Biochem Biophys Res Commun
; 244(1): 156-60, 1998 Mar 06.
Article
en En
| MEDLINE
| ID: mdl-9514902
Complementary DNA (cDNA) encoding human beta-amyloid precursor protein familial Alzheimer's disease (FAD) Swedish mutant (beta APPSM) 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 APPSM 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 APPSM 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridinas
/
Tiadiazoles
/
Transfección
/
Procesamiento Proteico-Postraduccional
/
Receptores Muscarínicos
/
Precursor de Proteína beta-Amiloide
/
Agonistas Muscarínicos
/
Mutación
Límite:
Animals
/
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos