CALPAIN IS ACTIVATED BY β-ADRENERGIC RECEPTOR STIMULATION UNDER HYPOXIC MYOCARDIAL CELL INJURY

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This study was undertaken to investigate the correlation between hypoxic cell injury and protease activity, as well as the effects of α₁-, and β-adrenergic blocking agents and calcium antagonists during hypoxia. Cell death during hypoxia rose to 80% after 6h. Calpain activity increased to 4 units during hypoxia, much higher than the 0.7 units seen in aerobic condition at 6h. This activity was markedly inhibited by calpain-specific inhibitor I (n-acetyl-leucyle-leucyle-norleucinal). α₁-adrenergic blocking agents did not affect calpain activity and cell death under hypoxia. On the other hand, β-adrenergic blocking agents and calcium antagonists suppressed the calpain activity and decreased cell death during hypoxia. These β-adrenergic blocking agents and calcium antagonists also inhibited intracellular calcium-influx during hypoxia. These results suggest the β-adrenergic receptor stimulation activates adenylate cyclase activity and enhances calcium-influx during hypoxia. The elevated intracellular calcium concentration then stimulates calpain activity under hypoxia. These results prove that β-adrenergic blocking agents and calcium antagonists prevent protein degradation during hypoxic cell injury.