EVIDENCE OF 2 MECHANISMS OF PROSTAGLANDIN RELEASE IN AN IN-VITRO MODEL OF MUSCLE DAMAGE - POSSIBLE THERAPEUTIC IMPLICATIONS

In spite of recent progress, treatment of muscle disease based on spec ific gene therapy is not yet available. An alternative approach is to develop treatment which affords non-specific protection against genera l factors involved in cell damage. This approach is used effectively t o prevent neuronal damage in experimental brain ischemia in animals an d has been proposed for human trials. The most effective intervention is the use of mild (35 degrees C) hypothermia. An in vitro model to st udy muscle cell damage employs the rat epitrochlearis muscle exposed t o low concentrations of 2:4-dinitrophenol, an uncoupler of oxidative p hosphorylation. The efflux of prostaglandin E(2) (PGE(2)) from the mus cle is used as an indicator of muscle damage. We now show that there a re two types of PGE(2) release. ''Basal'' efflux gradually declines wi th decreasing temperatures and is not affected by removal of calcium f rom the medium. The efflux of PGE(2) in response to metabolic stress i s dependent on the presence of calcium and is abolished by mild hypoth ermia of 35 degrees C. The latter effect suggests that cell death in m uscle and neurons have features in common and that muscle may be a use ful tissue in which to investigate this phenomenon further.