Hypoxic enhancement of quantal catecholamine secretion. Evidence for the involvement of amyloid β-peptides

Shafeena C. Taylor, Trevor F C Batten, Chris Peers

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Prolonged exposure to hypoxia (10% O 2) enhanced quantal catecholamine release evoked from O 2-sensing pheochromocytoma (PC 12) cells, as monitored using single-cell amperometric recordings. The enhancement of exocytosis was apparent after 12 h of hypoxia and was maximal at 24 h. Elevated levels of secretion were due to the emergence of a Ca 2+ influx pathway that persisted during complete blockade of known voltage-gated Ca 2+ channels. Secretion triggered by this Ca 2+ influx was severely reduced by known inhibitors of Alzheimer's amyloid β-peptides (AβPs), including an N terminus-directed monoclonal antibody. The enhancing effect on secretion of chronic hypoxia was mimicked closely by direct application of AβP to cells under normoxic conditions, although the effects of AβP were more rapid at onset, being maximal after only 6 h. The present results suggest that prolonged hypoxia can induce formation of Ca 2+-permeable AβP channels and that such induction can lead directly to excessive neurosecretion. This is a potential contributory factor to AβP pathophysiology following cerebral ischemia.

Original languageEnglish
Pages (from-to)31217-31222
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number44
DOIs
Publication statusPublished - 29 Oct 1999
Externally publishedYes

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