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Hypoxia Enhances [ 3 H]Noradrenaline Release Evoked by Nicotinic Receptor Activation from the Human Neuroblastoma SH‐SY5Y
Author(s) -
Wade J. A.,
Vaughan P. F. T.,
Peers C.
Publication year - 1998
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.1471-4159.1998.71041482.x
Subject(s) - chemistry , endocrinology , medicine , agonist , acetylcholine , egta , hypoxia (environmental) , sh sy5y , receptor , calcium , biochemistry , biology , cell culture , neuroblastoma , oxygen , genetics , organic chemistry
We have used the human sympathetic neuronal line SH‐SY5Y to investigate the effects of hypoxia on noradrenaline (NA) release evoked by either raised [K + ] o (100 m M ) or the nicotinic acetylcholine receptor (nAChR) agonist dimethylphenylpiperazinium iodide (DMPP). NA release was monitored by loading cells with [ 3 H]NA and collecting effluent fractions from perfused cells kept in a sealed perifusion chamber. Cells were challenged twice with either stimulus and release was expressed as that evoked by the second challenge as a fraction of that evoked by the first. K + ‐evoked release was unaffected by hypoxia (P o 2 ≅ 30–38 mm Hg), but release evoked by DMPP was significantly increased. For both stimuli, replacement of Ca 2+ o with 1 m M EGTA abolished NA release. K + ‐evoked release was also dramatically reduced in the presence of 200 µ M Cd 2+ to block voltage‐gated Ca 2+ channels, but DMPP‐evoked release was less affected. In hypoxia, DMPP‐evoked Cd 2+ ‐resistant NA release was dramatically increased. Our findings indicate that hypoxia increases NA release evoked from SH‐SY5Y cells in response to nAChR activation by increasing Ca 2+ influx through the nAChR pore, or by activating an unidentified Cd 2+ ‐resistant Ca 2+ ‐influx pathway. As acetylcholine is the endogenous transmitter at sympathetic ganglia, these findings may have important implications for sympathetic activity under hypoxic conditions.