Inhibition of mitochondrial Na(+)/Ca(2+) exchange by 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one attenuates free fatty acid efflux in rat cerebral cortex during ischemia-reperfusion injury.
We evaluated the effects of 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) (50 muM), a specific inhibitor of mitochondrial Na(+)/Ca(2+) exchange, applied topically onto rat cerebral cortex during ischemia-reperfusion injury. Free fatty acid (FFA) levels in cortical superfusates, withdrawn at 10 min intervals from bilateral cortical windows, were analyzed by high performance liquid chromatography. During a 20 min period of ischemia in control animals, there were significant increases in all FFAs. Following reperfusion, FFA levels remained significantly elevated. Application of CGP-37157 significantly inhibited effluxes of all FFAs during both ischemia and reperfusion. These data indicate that inhibition of mitochondrial Na(+)/Ca(2+) exchange likely prevented the activation of phospholipases that usually occurs following an ischemic insult as evidenced by its attenuation of FFA efflux.
Pilitsis
Julie G
JG
Department of Neurosurgery, Wayne State University, UHC-6E, 4201 St. Antoine, Detroit, MI 48201, USA.
Diaz
Fernando G
FG
O'Regan
Michael H
MH
Phillis
John W
JW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects* / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D018696:Neuroprotective Agents; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; C079032:CGP 37157; D012964:Sodium; D010741:Phospholipases A; D002118:Calcium