The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil.
Cerebral ischemia of 5 min duration was induced in unanesthetized Mongolian gerbils by bilateral occlusion of the carotid arteries. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity following ischemia and by a histopathological assessment of the extent of CA1 hippocampal pyramidal cell injury and loss 5 days after ischemia. The A2a adenosine receptor selective antagonists 8-(3-chlorostyryl) caffeine (CSC; 0.1 mg/kg i.p.) and 4-amino-1-phenyl[1,2,4]-triazolo[4,3-a] quinoxaline (CP 66,713; 0.1 mg/kg i.p.) reduced the extent of ischemia-induced injury. An A1 selective receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1.0 mg/kg i.p.), enhanced ischemia-evoked injury. These results suggest that adenosine A2a receptor antagonists may be useful for the prevention of cerebral injuries resulting from stroke or cardiac arrest.
Phillis
J W
JW
Department of Physiology, Wayne State Univesity School of Medicine, Detroit, MI 48201, USA.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D002339:Carotid Arteries / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000737:chemistry / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000503:physiopathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D008124:Locomotion / Q000187:drug effects; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy*; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D011719:Pyrazines; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; C072107:CP 66713; C051360:1,3-dipropyl-8-cyclopentylxanthine; D004121:Dimethyl Sulfoxide