title: Muscarinic control of amyloid precursor protein secretion in rat cerebral cortex and cerebellum.
abstract: It was previously shown by us and by others that activation of muscarinic acetylcholine receptors evoke amyloid precursor protein (APP) secretion in various cell lines. Here we examined if such muscarinic control of APP secretion occurs also in normal brain tissues. We found that the secretion of APP from rat cerebrocortical slices (rich in M1 receptors) was significantly increased by K+ depolarization, the non-selective agonist, carbachol (CCh), and the M1-selective agonist, AF102B. CCh also increased APP secretion from cerebellar slices (rich in M2 receptors) while AF102B had no significant effect in this brain region. Despite of its stimulatory effect on APP release in the cerebellum, CCh had no effect on phosphoinositide (PI) metabolism in this brain region. In the cerebral cortex PI metabolism was significantly increased by CCh but only partially increased by AF102B. These results suggest that APP secretion in the brain is mediated via muscarinic receptors. In the cerebral cortex APP secretion seems to be regulated via M1 receptors. Our results also suggest that PI metabolism is not a pronounced step in mediating APP processing.
authors.affiliation: Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Pittel
authors.forename: E
authors.initials: E
authors.lastname: Heldman
authors.forename: J
authors.initials: J
authors.lastname: Barg
authors.forename: R
authors.initials: R
authors.lastname: Haring
authors.forename: A
authors.initials: A
authors.lastname: Fisher
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D002217:Carbachol