Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins.
We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia.
Kuwaki
T
T
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Satoh
H
H
Ono
T
T
Shibayama
F
F
Yamashita
T
T
Nishimura
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology
D002148:Calmodulin-Binding Proteins; D002966:Clathrin; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; C035100:nilvadipine; D009553:Nimodipine; D009529:Nicardipine; D009543:Nifedipine