title: Dopamine release from canine striatum following global cerebral ischemia/reperfusion.
abstract: The elevation of extracellular dopamine (DA) levels in the striatum of experimental animals subjected to ischemic insult has been well documented. The contribution of excessive DA to neuronal damage can be inferred from the ability of DA antagonists, as well as selective destruction of dopaminergic tracts, to confer neuroprotection in models of ischemia. In the current study, we report an enhanced releasability of preloaded [3H]DA in response to either elevated potassium or N-methyl-D-aspartate (NMDA) from striatal slices of beagles that had experienced 10 min of ischemia induced by cardiac arrest. The elevation in sensitivity to potassium stimulation was transient, approaching control levels after 30 min of reperfusion. In contrast, release stimulated by NMDA was elevated immediately after cardiac arrest and remained elevated for as long as 24 h of reperfusion. Release stimulated by NMDA was enhanced by glycine (Gly) and inhibited by MK801, consistent with mediation through the NMDA receptor/channel complex. The increased sensitivity of DA release, coupled with the high levels of excitatory amino acids (EAAs), including glutamate (Glu), aspartate (Asp) and Gly in ischemic brain, probably contribute to the extensive neuronal cell damage.
authors: Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
authors: L L
authors: LL
authors: Werling
authors: H M
authors: HM
authors: Jacocks
authors: R E
authors: RE
authors: Rosenthal
authors: G
authors: G
authors: Fiskum
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004285:Dogs; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006324:Heart Arrest, Induced; D016202:N-Methylaspartate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D016202:N-Methylaspartate; D011188:Potassium; D004298:Dopamine