Dopamine induces Ca2+ signaling in astrocytes through reactive oxygen species generated by monoamine oxidase.
Dopamine is a neurotransmitter that plays a major role in a variety of brain functions, as well as in disorders such as Parkinson disease and schizophrenia. In cultured astrocytes, we have found that dopamine induces sporadic cytoplasmic calcium ([Ca(2+)](c)) signals. Importantly, we show that the dopamine-induced calcium signaling is receptor-independent in midbrain, cortical, and hippocampal astrocytes. We demonstrate that the calcium signal is initiated by the metabolism of dopamine by monoamine oxidase, which produces reactive oxygen species and induces lipid peroxidation. This stimulates the activation of phospholipase C and subsequent release of calcium from the endoplasmic reticulum via the inositol 1,4,5-trisphosphate receptor mechanism. These findings have major implications on the function of astrocytes that are exposed to dopamine and may contribute to understanding the physiological role of dopamine.
Vaarmann
Annika
A
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
Gandhi
Sonia
S
Abramov
Andrey Y
AY
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D008995:Monoamine Oxidase / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D053496:Inositol 1,4,5-Trisphosphate Receptors; D008055:Lipids; D017382:Reactive Oxygen Species; D008995:Monoamine Oxidase; D010100:Oxygen; D002118:Calcium; D004298:Dopamine