title: cAMP production mediated through P2Y(11)-like receptors in rat striatum due to severe, but not moderate, carbon monoxide poisoning.
abstract: We examined the effect of carbon monoxide (CO) poisoning on the production of cAMP, an intracellular second messenger, in rat striatum in terms of extracellular cAMP, which is highly correlated with intracellular cAMP, by using microdialysis. Severe poisoning due to 3000ppm CO, but not moderate poisoning due to 1000ppm CO, caused an increase in cAMP, which was susceptible to a voltage-dependent Na(+) channel blocker, tetrodotoxin, and more profound than that under comparable hypoxia caused by 5% O(2). These results were similar to our previous findings on the production of hydroxyl radical ((•)OH), suggesting a close relationship between cAMP and (•)OH production. The increase in cAMP was suppressed by a non-selective purine P2 receptor antagonist, suramin. However, other non-selective P2 receptor antagonists, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and reactive blue 2, exhibited no effect and weak non-significant suppression, respectively. A P2Y(11) receptor antagonist, NF157, dose-dependently suppressed the increase in cAMP, although rats lack the P2Y(11) receptor. These results suggest that a threshold for cAMP production mediated through P2Y(11)-like receptors following depolarization triggered by Na(+) influx exists in rat striatum during CO poisoning, and that the threshold is reached only in cases of severe CO poisoning. It is also likely that the threshold is related to the generation of (•)OH, contributing to the toxicity of CO in the brain.
authors.affiliation: Department of Forensic Medicine, Tokyo Medical University, Tokyo 160-8402, Japan. s-hara@tokyo-med.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hara
authors.forename: Hajime
authors.initials: H
authors.lastname: Mizukami
authors.forename: Fumi
authors.initials: F
authors.lastname: Kuriiwa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Mukai
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000633:toxicity*; D002249:Carbon Monoxide Poisoning / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D018048:Receptors, Purinergic P2; D017665:Hydroxyl Radical; D002248:Carbon Monoxide; D000242:Cyclic AMP