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

The effects of chronic hypoxia (2.5% O-2, 24 h) on [H-3]noradrenaline ([H-3 ]NA) release evoked from human neuroblastoma SH-SY5Y cells by depolarisatio n and by activation of muscarinic receptors was investigated. Depolarizatio n of cells with 100 mM K+ evoked [H-3]NA release, and chronic hypoxia enhan ced this release significantly. in fluorimetric studies, the Kt-evoked rise s of [Ca2+](i) observed in response to 100 mM K+ were also significantly en hanced. Muscarine-evoked [H-3]NA release was also dramatically enhanced by chronic hypoxia. However. muscarine-induced release of Ca2+ from intracellu lar stores and subsequent capacitative Ca2+ entry was unaffected. The prote in kinase C inhibitors GF 109 203X and RO-31-8220 did not prevent the enhan cement of muscarine-evoked release caused by chronic hypoxia. These finding s indicate that chronic hypoxia increases release of [H-3]NA from human neu roblastoma SH-SY5Y cells. Enhancement of K+-evoked release was attributable to an enhancement of depolarisation-mediated Ca2+ influx. In contrast, the larger enhancement of muscarine-evoked [H-3]NA release was not due to grea ter release of Ca2+ from internal stores, nor due from internal stores, nor due of sympathetic output. Furthermore, it is not attributable to activati on of protein kinase C. These findings suggest that enhancement of sympathe tis output, known to occur following prolonged hypoxia, may be mediated in part by enhancement of exocytosis. Elsevier Science B.V. All rights reserve d.