BEPRIDIL REDUCING LEVOTHYROXINE-INDUCED ENHANCEMENT OF MITOCHONDRIA CA2-ATPASE ACTIVITY IN RAT CEREBRUM( MG2+)

AIM: To study if bepridil (Bep) could affect the enhancement of activi ty of cerebral mitochondria Ca2+ Mg2+-ATPase caused by levothyroxine ( Lev) in relation to ischemic overload calcium cerebrum injury. METHODS : The experimental hyperthyroidism model with ischemic cerebrum was de veloped in rats by ig Lev 1 mg . kg(-1). d(-1) for 7 d. Ca2+ Mg2+-ATPa se activity and its kinetic parameters were assayed. RESULTS: The acti vity, V-max and K-m of cerebral mitochondria Ca2+ Mg2+-ATPase in contr ol rats were 3.1+/-0.8, 5.1+/-2.3 mmol . P-i . h(-1)/g protein and 0.8 1+/-0.08 mmol . L(-1) (ATP) respectively, whereas those of hyperthyroi d rats were significantly altered to 4.6+/-0.5, 8.5+/-1.9 mmol . P-i . h(-1)/g protein and 0.49+/-0.11 mmol . L(-1) (ATP) respectively. Afte r treated with Bep 10 or 20 mg . kg(-1). d(-1) ig for 3 d, allabove 3 parameters of the enzyme were very significantly reduced vs those of e ither control or hyperthyroid. CONCLUSION: Bep, via decreasing Ca2+ M( 2+)-ATPase activity and increasing the affinity of Ca2+ Mg2+-ATPase to ATP, could prevent rat cerebrum from ATP depletion and ischemic overl oad calcium injury.