title: Amyloid beta protein (25-35) stimulation of phospholipase C in LA-N-2 cells.
abstract: The amyloid beta protein (25-35) stimulated appearance of 3H-inositol phosphates from [3H]inositol-prelabeled LA-N-2 cells was investigated. This stimulation was unaltered by extra- and intracellular calcium chelators in a calcium-free medium or by several protein kinase inhibitors. This phospholipase C stimulation by amyloid beta protein appeared to be pertussis toxin sensitive. It is possible that this phospholipase C stimulation by amyloid beta protein is a receptor-mediated process. This possibility is based on two related observations. The stimulation is ablated by the presence of conventional antagonists for metabotropic, adrenergic, and bombesin agonists. The IC50 values were 12 microM for propranolol, 15 microM for AP-3, and 25 nM for [Tyr4,D-Phe12]bombesin. Additional support comes from results of desensitization and resensitization experiments. Amyloid beta protein stimulation of phospholipase C was absent from LA-N-2 cells previously treated with norepinephrine, trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), bombesin, or amyloid beta peptide. In a similar manner, LA-N-2 cells previously treated with amyloid beta protein were no longer responsive to norepinephrine, t-ACPD, or bombesin. The responsiveness to amyloid beta protein returned, subsequent to a period of resensitization for the individual agonists. It is suggested that this observed amyloid beta protein stimulation of phospholipase C may be responsible for the elevated quantity of inositol seen in the brains of Alzheimer's disease patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
authors.forename: I N
authors.initials: IN
authors.lastname: Singh
authors.forename: G
authors.initials: G
authors.lastname: Sorrentino
authors.forename: J N
authors.initials: JN
authors.lastname: Kanfer
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D037342:Pertussis Toxin; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012680:Sensitivity and Specificity; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D000316:Adrenergic alpha-Agonists; D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; C074636:amyloid beta-protein (25-35); D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D011494:Protein Kinases; D010738:Type C Phospholipases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D001839:Bombesin; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine