ISSN:
1432-0878
Schlagwort(e):
Muscle damage
;
Cardiac muscle
;
Calcium
;
Phospholipase A2
;
Lipoxygenase
;
Cyclo-oxygenase
;
Rana ttemporaria
;
Mouse
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Biologie
,
Medizin
Notizen:
Summary This study compares the action of inhibitors of the eicosanoid cascade on calcium-induced myofilament damage in cardiac muscle of the perfused frog heart and incubated frog ventricle slices, and in skeletal muscle of incubated mammalian diaphragm and isolated and saponin-skinned amphibian pectoris cutaneous muscle. Mepacrine (10-5M) and indomethacin (3×10-6M) protected completely against myofilament damage induced by entry of calcium in the ‘calcium-paradox’ in frog heart. However, inhibition of phospholipase A2 (PLA2) (with chlorpromazine, 2×10-4M, or mepacrine, 10-5M, 5x10-5M), of cyclo-oxygenase enzymes (with indomethacin, 3x10-6M to 10-5M or BW755C, 3.8x10-4M), or of lipoxygenase enzymes (with BW755C, 3.8x10-4M or nordihydroguaiaretic acid, 2x10-6M or 5x10-6M) all failed in intact cardiac or skeletal muscle cells to prevent the myofilament damage that is rapidly triggered by 10-2M caffeine, 6x10-6M ruthenium red, 10-4M DNP or 5 μg ml-1 A23187. These agents also failed completely to protect against myofilament damage in saponin-skinned amphibian skeletal muscle when [Ca]i was raised to 8x10-6M. Thus, inhibition of PLA2 does not protect the myofilament apparatus against calcium released intracellularly, and it is suggested that mepacrine and indomethacin can block entry of calcium in the calcium-paradox in the amphibian heart. Chlorpromazine (2x10-4M) and mepacrine (10-3M) at zero [Ca] caused severe myofilament damage in skinned muscle, possibly due to an effect on membranes. Since inhibitors of PLA2 and of lipoxygenases prevent efflux of creatine kinase and sarcolemma damage in mammalian skeletal muscle, it is evident that experimentally-induced rises in [Ca]i (by caffeine or A23187) can trigger two separate pathways: (i) PLA2 and the arachidonic acid cascade which culminate in membrane damage, and (ii) a different, Ca-activated system that causes rapid damage of myofilaments.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00222303
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