Phospholipase A2 activation influences the processing and secretion of the amyloid precursor protein.
The phospholipase A2 (PLA2) inhibitors quinacrine, manoalide and scalaradial inhibit the carbachol-stimulated secretion of the amyloid precursor protein (APP) from cells transfected with the human m1 muscarinic receptor. Conversely, activation of PLA2 by melittin increases secretion of an apparently immature species of APP from these cells. These results implicate PLA2 in regulating APP processing and secretion, which may have important implications for understanding the pathogenesis of Alzheimer's Disease.
Emmerling
M R
MR
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48106.
Moore
C J
CJ
Doyle
P D
PD
Carroll
R T
RT
Davis
R E
RE
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002217:Carbachol / Q000494:pharmacology; D006224:Cricetinae; D004789:Enzyme Activation; D006718:Homosteroids; D008555:Melitten / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011499:Protein Processing, Post-Translational; D011796:Quinacrine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism; D054830:Sesterterpenes; D013729:Terpenes / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D006718:Homosteroids; D011976:Receptors, Muscarinic; D054830:Sesterterpenes; D013729:Terpenes; D008555:Melitten; C071197:scalaradial; D002217:Carbachol; C045673:manoalide; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine