Beta-amyloid1-40 inhibits electrically stimulated release of [3H]norepinephrine and enhances the internal calcium response to low potassium in rat cortex: prevention with a free radical scavenger.
We examined the effects of beta-amyloid1-40 (A beta 1-40) on the electrically stimulated release of [3H]norepinephrine (NE) and the potassium chloride (KCl)-evoked increases in intrasynaptosomal calcium ([Ca2+]i) from rat brain cortical slices and synaptosomes, respectively. The results show that 3nM A beta 1-40 decreased electrically stimulated [3H]NE release approximately 50%, and the same concentration of A beta 1-40 increased [Ca2+]i by 78% above control during low level (10 mM) KCl depolarization. Complete prevention of both effects was observed when the free radical scavenger 1mM N-tert-butyl-alpha-phenylnitrone (PBN) was present. Also, when PBN was exposed to the slice first and then followed by A beta 1-40, the inhibition of [3H]NE was blocked. Alone, PBN had no effect in either paradigm. Our experiments show that 3 nM A beta 1-40 allows a PBN-sensitive free radical to deleteriously effect both evoked [3H]NE release and [Ca2-]i regulation in rat cortical slices and synaptosomes.
Li
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Hoechst Marion Roussel Inc., Somerville, NJ 08876, USA.
Smith
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CP
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D014316:Tritium; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine