Intrastriatal microinjection of sodium nitroprusside induces cell death and reduces binding of dopaminergic receptors.
Rat striatum was microinjected with 50 nmol sodium nitroprusside (SNP) and neural cell death as well as the binding of dopaminergic receptors were followed for 24 h after the infusion using TTC staining, cresyl violet staining, and quantitative autoradiography. Striatal cell death was observed 3 h after the infusion of SNP. A widespread area of cell death, including part of the cerebral cortex, was seen at 24 h after the infusion. A decrease of more than 80% in dopamine D1 receptor binding was seen in rat brain slices prepared 2 h after the infusion of SNP, whereas only a slight decrease in dopamine D2 receptor binding and almost no changes in dopamine transporter binding were observed. One day after the infusion, less than 10% of the binding of all three types of dopaminergic receptors remained in a widespread area in the infused side of the striatum and part of the cerebral cortex. Microinjection of either NOC-18 (50 nmol), another type of NO donor, or sodium cyanide (50 nmol) did not caused cell death. In addition, microinjection of FeCl2 (50 nmol) into the striatum caused cell death and reduction in dopamine D() receptor binding. These results suggest that iron-related radical reactions, but not NO itself, might have important roles on SNP-caused cell death. The current receptor binding study also indicated that dopamine D1 receptor binding is the most sensitive indicator for detection of cell death or cell damage induced by radical reactions in the rat striatum.
Yanamoto
Kazuhiko
K
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Hosoi
Rie
R
Uesaka
Yumi
Y
Abe
Kohji
K
Tsukada
Hideo
H
Inoue
Osamu
O
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005296:Ferrous Compounds / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000633:toxicity*; D009603:Nitroso Compounds / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D001552:Benzazepines; D018492:Dopamine Antagonists; D005296:Ferrous Compounds; C093285:NOC 18; D009603:Nitroso Compounds; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D009599:Nitroprusside; D009569:Nitric Oxide; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D012966:Sodium Cyanide; C029451:ferrous chloride