Different mechanisms mediate structural changes and intracellular enzyme efflux following damage to skeletal muscle.
Cellular damage, induced by either A23187 (2 X 10(-5)M) or 2,4-dinitrophenol (DNP) (10(-3)M), has been studied in incubated mouse soleus muscle and has been monitored by electron microscopy and measurement of creatine kinase (CK) efflux. CK efflux induced by DNP was dependent on extracellular Ca, whereas the characteristic myofilament breakdown was not. Chlorpromazine (2 X 10(-4)M; an inhibitor of phospholipase A (PLA2] or 5 X 10(-6)M-nordihydroguaiaretic acid (NDGA) (a lipoxygenase inhibitor) almost completely inhibited CK efflux, following treatment with either A23187 or DNP, but did not affect myofilament damage. It is concluded that there are at least two separate pathways in cellular damage: (1) PLA2 activation and lipoxygenase activity culminating in sarcolemma damage and (2) a system that produces characteristic destruction of the myofilament apparatus.
D019297:2,4-Dinitrophenol; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009132:Muscles / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D014475:Uncoupling Agents / Q000494:pharmacology
D004140:Dinitrophenols; D014475:Uncoupling Agents; D000001:Calcimycin; D009637:Masoprocol; D003402:Creatine Kinase; D019297:2,4-Dinitrophenol; D002118:Calcium; D002746:Chlorpromazine