Premium
Amyloid β Protein (25–35) Stimulation of Phospholipase C in LA‐N‐2 Cells
Author(s) -
Singh Indrapal N.,
Sorrentino Giuseppe,
Kanfer Julian N.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69010252.x
Subject(s) - bombesin , stimulation , phospholipase , phospholipase c , medicine , endocrinology , inositol , protein kinase c , amyloid (mycology) , amyloid precursor protein , inositol phosphate , biology , chemistry , biochemistry , receptor , alzheimer's disease , signal transduction , neuropeptide , enzyme , disease , botany
The amyloid β protein (25–35) stimulated appearance of 3 H‐inositol phosphates from [ 3 H]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 β protein appeared to be pertussis toxin sensitive. It is possible that this phospholipase C stimulation by amyloid β 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 IC 50 values were 12 µ M for propranolol, 15 µ M for AP‐3, and 25 n M for [Tyr 4 , d ‐Phe 12 ]bombesin. Additional support comes from results of densensitization and resensitization experiments. Amyloid β 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 β peptide. In a similar manner, LA‐N‐2 cells previously treated with amyloid β protein were no longer responsive to norepinephrine, t‐ACPD, or bombesin. The responsiveness to amyloid β protein returned, subsequent to a period of resensitization for the individual agonists. It is suggested that this observed amyloid β protein stimulation of phospholipase C may be responsible for the elevated quantity of inositol seen in the brains of Alzheimer's disease patients.