MUSCARINIC CONTROL OF AMYLOID PRECURSOR PROTEIN SECRETION IN RAT CEREBRAL-CORTEX AND CEREBELLUM

It was previously shown by us and by others that activation of muscari nic acetylcholine receptors evoke amyloid precursor protein (APP) secr etion in various cell lines. Here we examined if such muscarinic contr ol of APP secretion occurs also in normal brain tissues. We found that the secretion of APP from rat cerebrocortical slices (rich in M1 rece ptors) was significantly increased by K+ depolarization, the non-selec tive agonist, carbachol (CCh), and the M1-selective agonist, AF102B. C Ch also increased APP secretion from cerebellar slices (rich in M2 rec eptors) while AF102B had no significant effect in this brain region. D espite of its stimulatory effect on APP release in the cerebellum, CCh had no effect on phosphoinositide (PI) metabolism in this brain regio n. In the cerebral cortex PI metabolism was significantly increased by CCh but only partially increased by AF102B. These results suggest tha t APP secretion in the brain is mediated via muscarinic receptors. In the cerebral cortex APP secretion seems to be regulated via M1 recepto rs. Our results also suggest that PI metabolism is not a pronounced st ep in mediating APP processing.