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Release of dopamine and norepinephrine by hypoxia from PC-12 cells
Abstract
We examined the effects of hypoxia on the release of dopamine (DA) and norepinephrine (NE) from rat pheochromocytoma 12 (PC-12) cells and assessed the involvement of Ca2+ and protein kinases in stimulus-secretion coupling. Catecholamine release was monitored by microvoltammetry using a carbon fiber electrode as well as by HPLC coupled with electrochemical detection (ECD). Microvoltammetric analysis showed that hypoxia-induced catecholamine secretion (PO2 of medium approximately 40 mmHg) occurred within 1 min after the onset of the stimulus and reached a plateau between 10 and 15 min. HPLC-ECD analysis revealed that, at any level of PO2, the release of NE was greater than the release of DA. In contrast, in response to K+ (80 mM), DA release was approximately 11-fold greater than NE release. The magnitude of hypoxia-induced NE and DA releases depended on the passage, source, and culture conditions of the PC-12 cells. Omission of extracellular Ca2+ or addition of voltage-gated Ca2+ channel blockers attenuated hypoxia-induced release of both DA and NE to a similar extent. Protein kinase inhibitors, staurosporine (200 nM) and bisindolylmaleimide I (2 microM), on the other hand, attenuated hypoxia-induced NE release more than DA release. However, protein kinase inhibitors had no significant effect on K+-induced NE and DA releases. These results demonstrate that hypoxia releases catecholamines from PC-12 cells and that, for a given change in PO2, NE release is greater than DA releas…
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“Furthermore, hypoxia and HIFs are important regulators of the synthesis (Schnell et al., 2003) and secretion (Kumar et al., 1998) of catecholamines, which are key SNS neurotransmitters.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Kumar et al., 1998
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References 35 · Cited by 87
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Metadata
- Authors
- Kumar, G. K., Overholt, J. L., Bright, G. R., Hui, K. Y., Lu, H., Gratzl, M., & Prabhakar, N. R.
- Affiliations
- Departments of Biochemistry,
- Physiology and Biophysics,
- Anatomy, and
- Case Western Reserve University (US)
- Biomedical Engineering, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 1998-06-01
- Volume
- 274
- Issue
- 6
- Pages
- C1592-C1600
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2336038108
- Cited by
- 87
- References
- 35
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 5
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k04hl002599-03, 5r01hl045780-05)
- National Heart, Lung, and Blood Institute (HL-25830, P01HL025830, HL45780, HL02599)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- hypoxia, dopamine release, noradrenaline release, catecholamine release, PC12 cells, pheochromocytoma cells, calcium-dependent secretion, voltage-gated calcium channels, protein kinases, staurosporine, bisindolylmaleimide I, potassium-evoked release, stimulus-secretion coupling
- MeSH terms
- Animals, Calcium Channel Blockers, Cell Survival, Chromatography, High Pressure Liquid, Dopamine, Enzyme Inhibitors, Indoles, Maleimides, Microelectrodes, Norepinephrine, Oxygen, Potassium, Protein Kinases, Calcium Channels, Cell Hypoxia, PC12 Cells, Staurosporine, Protein Kinase Inhibitors, Rats
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- Kumar, G. K., Overholt, J. L., Bright, G. R., Hui, K. Y., Lu, H., Gratzl, M., & Prabhakar, N. R. (1998). Release of dopamine and norepinephrine by hypoxia from PC-12 cells. American Journal of Physiology-Cell Physiology. https://doi.org/10.1152/ajpcell.1998.274.6.c1592