Hypoxic enhancement of evoked noradrenaline release from the human neuroblastoma SH-SY5Y

Brain Research. Molecular Brain Research
N J WebsterC Peers

Abstract

The effects of chronic hypoxia (2.5% O(2), 24 h) on [3H]noradrenaline ([3H]NA) release evoked from human neuroblastoma SH-SY5Y cells by depolarisation and by activation of muscarinic receptors was investigated. Depolarization of cells with 100 mM K(+) evoked [3H]NA release, and chronic hypoxia enhanced this release significantly. In fluorimetric studies, the K(+)-evoked rises of [Ca(2+)](i) observed in response to 100 mM K(+) were also significantly enhanced. Muscarine-evoked [3H]NA release was also dramatically enhanced by chronic hypoxia. However, muscarine-induced release of Ca(2+) from intracellular stores and subsequent capacitative Ca(2+) entry was unaffected. The protein kinase C inhibitors GF 109 203X and RO-31-8220 did not prevent the enhancement of muscarine-evoked release caused by chronic hypoxia. These findings indicate that chronic hypoxia increases release of [3H]NA from human neuroblastoma SH-SY5Y cells. Enhancement of K(+)-evoked release was attributable to an enhancement of depolarisation-mediated Ca(2+) influx. In contrast, the larger enhancement of muscarine-evoked [3H]NA release was not due to greater release of Ca(2+) from internal stores, nor due to enhanced Ca(2+) influx. Furthermore, it was not attribut...Continue Reading

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