MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPES ASSOCIATED WITH RELEASE OF ALZHEIMER AMYLOID PRECURSOR DERIVATIVES ACTIVATE MULTIPLE SIGNAL-TRANSDUCTION PATHWAYS

Five subtypes of muscarinic acetylcholine receptors have been identified and designated m1-m5. The m1 and m3 receptors have recently been shown to stimulate APP processing. The m1 and m3 receptors couple to a variety of signal transduction pathways in both tissue slices and a variety of cell lines endogenously expressing either or both subtypes. In contrast, the m2 and m4 receptors have been primarily associated with inhibition of adenylate cyclase. We have transfected all five subtypes of muscarinic receptors into a variety of mammalian cell lines in order to investigate the signaling associated with single receptor subtypes. The m1, m3, or m5 receptors stimulate phospholipase A(2), C, and D, adenylate cylase, receptor-operated calcium channels, and tyrosine kinase activity simultaneously. The m2 or m4 receptor inhibits cAMP accumulation and augments a previously stimulated release of arachidonic acid and calcium influx.