Protective action of calcium channel blockers on Na+,K+-ATPase in gerbil cerebral cortex following ischemia.
The present study was initiated to determine whether pretreatment of gerbils with calcium channel blockers, flunarizine and verapamil would prevent injury to cerebral ATPases following secondary ischemia consisting of 60-min bilateral clamping of the carotids followed by 40 min of reperfusion. The sequence of ischemia produced a deficit in Na+,K+-ATPase activity without influencing Ca++,Mg++- or Mn++-sensitive ATPases. Pretreatment with flunarizine significantly prevented the damage to Na+,K+-ATPase while the effect of verapamil was marginal. Verapamil, along with dimethylsulfoxide (DMSO), reduced the mortality rate of gerbils subjected to the paradigm of ischemia. When added directly to the cerebral fractions in vitro the two calcium channel blockers inhibited Na+,K+-ATPase alone. Flunarizine was more potent in vitro than verapamil.
Palmer
G C
GC
Frist-Massey Neurological Institute, Nashville, Tennessee.
Palmer
S J
SJ
Christie-Pope
B C
BC
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D005444:Flunarizine / Q000494:pharmacology* / Q000627:therapeutic use; D005849:Gerbillinae; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D005444:Flunarizine