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 release. It is suggested that protein kinases are involved in the enhanced release of NE during hypoxia.

• Authors: G K Kumar, J L Overholt, G R Bright, K Y Hui, H Lu, M Gratzl, N R Prabhakar
• Journal: The American journal of physiology (Am J Physiol) Vol. 274 Issue 6 Pg. C1592-600 (06 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9611124 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channel Blockers
• Calcium Channels
• Enzyme Inhibitors
• Indoles
• Maleimides
• Protein Kinase Inhibitors
• Protein Kinases
• Staurosporine
• bisindolylmaleimide
• Potassium
• Oxygen
• Dopamine
• Norepinephrine

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (physiology)
• Cell Hypoxia
• Cell Survival
• Chromatography, High Pressure Liquid
• Dopamine (metabolism)
• Enzyme Inhibitors (pharmacology)
• Indoles (pharmacology)
• Maleimides (pharmacology)
• Microelectrodes
• Norepinephrine (metabolism)
• Oxygen (administration & dosage)
• PC12 Cells (metabolism)
• Potassium (pharmacology)
• Protein Kinase Inhibitors
• Protein Kinases (metabolism)
• Rats
• Staurosporine (pharmacology)