title: Specific ligand for a central type prostacyclin receptor attenuates neuronal damage in a rat model of focal cerebral ischemia.
abstract: The neuroprotective effect of a central type prostacyclin receptor ligand was examined in a rat model of focal cerebral ischemia. Under halothane anesthesia, male Sprague-Dawley rats were subjected to left middle cerebral artery occlusion. A selective central type prostacyclin receptor ligand, 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester, or a peripheral type prostacyclin receptor ligand, iloprost methylester, were administered intravenously immediately after ischemia. Twenty-four hours after ischemia, brain damage was evaluated. In separate experiments, concentrations of 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin in ischemic brain tissue were measured by injection of a tritium labeled compound. Treatment with 15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester (0.03 mg/kg) significantly (P<0.05) reduced the volume of brain damage by 35%. With this treatment, the concentration of this compound in the brain was more than 10 nM. Treatment with iloprost methylester did not show a neuroprotective effect. These results indicated that activation of a central type prostacyclin receptor attenuates ischemic brain damage. The present study demonstrated that the intravenous application of a central type prostacyclin receptor ligand could be a novel therapeutic agent for acute stroke.
authors.affiliation: The Medical and Pharmacological Research Center Foundation, Wo32, Inoyama-cho, Hakui-Shi, Ishikawa, 925-0613, Japan. takamatsu@mprcf.or.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yilong
authors.initials: Y
authors.lastname: Cui
authors.forename: Yosky
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hosoya
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000032:analysis; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000145:classification / Q000378:metabolism*
chemical_list: C449380:15-deoxy-(16-m-tolyl)-17,18,19,20-tetranorisocarbacyclin methylester; C401841:15-deoxy-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin; D008024:Ligands; D018696:Neuroprotective Agents; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D011464:Epoprostenol