Amyloid precursor protein secretion via muscarinic receptors: Reduced desensitization using the m1-selective agonist AF102B

Rachel Haring, David Gurwitz, Jacob Barg, Ronit Pinkas-Kramarski, Eliahu Heldman, Zipora Pittel, Ada Wengier, Haim Meshulam, Daniele Marciano, Yishai Karton, Abraham Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

Secretion of amyloid precursor protein (APP) by cultured cells is coupled to several receptors, including m1 muscarinic (m1AChR), and is associated with decreased production of βA4 amyloid. Secreted and cell-associated APP levels were measured in m1AChR-transfected PC12 cells stimulated with the non-selective agonist carbachol or the M1-selective agonist, AF102B. Secreted APP levels following stimulation with AF102B (5-60 min) were about half compared with carbachol. Yet, following 24 h stimulation with carbachol or AF102B, cell-associated APP levels were similarly decreased. This may be associated with a smaller reduction in APP secretion following 24 h stimulation with AF102B as compared with carbachol. AF102B may therefore have an advangage over non-selective muscarinic ligands for sustained decrease of cell-associated APP.

Original languageEnglish
Pages (from-to)652-658
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume203
Issue number1
DOIs
StatePublished - 30 Aug 1994
Externally publishedYes

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