Sensitivities of benzodiazepine receptor binding and muscarinic acetylcholine receptor binding for the detection of neural cell death caused by sodium nitroprusside microinjection in rat brain.
Sodium nitroprusside (SNP) was microinjected into rat cerebral cortex and changes in muscarinic acetylcholine receptor (mAChR) binding and benzodiazepine receptor (BZR) binding were followed for 24 h after the infusion using [(3)H]-N-methyl-4-piperidyl benzilate ([(3)H]-NMPB) and [(3)H]-flumazenil, respectively, as a radioligand. The microinjection of SNP dose-dependently caused significant neural cell death 3 h after infusion, with the area of cell death becoming extensive 24 h after infusion. Neither SIN-1 nor NOC-18, other types of NO donors, caused neural cell death. Together with the result that deferoxamine, an iron-chelating agent, protected SNP-induced brain injury indicated important roles of iron-related radicals in SNP cytotoxicity in rat brain. In vitro [(3)H]-NMPB binding was significantly reduced in parallel with the time course of neural cell death detected by TTC staining and Nissl staining. In contrast, [(3)H]-flumazenil binding was essentially unaltered during the 24-h period after the SNP infusion. Similar results were observed in in vivo binding experiments. In vivo [(3)H]-NMPB binding was found to be much more sensitive at detecting cell death caused by SNP. On the other hand, [(3)H]-flumazenil binding in vivo was relatively insensitive to SNP-induced cell death. These results indicate that mAChR binding may be superior to BZR binding for detecting cell death in brain tissue, in contrast to what was previously thought.
Inoue
Osamu
O
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka 565-0871, Japan. inoue@sahs.med.osaka-u.ac.jp
Yanamoto
Kazuhiko
K
Fujiwara
Yoshiko
Y
Hosoi
Rie
R
Kobayashi
Kaoru
K
Tsukada
Hideo
H
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D009599:Nitroprusside