Horrobin D F, Morgan R, Karmali R A, Manku M S, Karmazyn M, Ally A, Mtabaji J P
Med Hypotheses. 1977 Jul-Aug;3(4):150-3. doi: 10.1016/0306-9877(77)90064-0.
There is good evidence that abnormal calcium accumulation may be a final common pathway of muscle degeneration in the muscular dystrophies. Prostaglandins are able to promote calcium entry into cells and excess prostaglandin activity coupled with a defect in intracellular calcium release could cause toxic accumulations of calcium in intracellular organelles such as mitochondria. Serotonin stimulates prostaglandin synthesis while tricyclic antidepressants inhibit calcium release from intracellular organelles thus possibly accounting for the models of muscular dystrophy reported using this combination. The prostaglandin/calcium hypothesis can account for the effects of vitamin E, steroids and local anaesthetic-like drugs in muscular dystrophy. Since many drugs already in clinical use for other purposes can be used to control prostaglandin synthesis or action this hypothesis has immediate potential clinical applications.
有充分证据表明,钙异常蓄积可能是肌营养不良症中肌肉变性的最终共同途径。前列腺素能够促进钙进入细胞,而前列腺素活性过高以及细胞内钙释放缺陷可能导致钙在细胞内细胞器(如线粒体)中产生毒性蓄积。血清素刺激前列腺素合成,而三环类抗抑郁药抑制细胞内细胞器释放钙,这可能解释了使用这种组合报道的肌营养不良症模型。前列腺素/钙假说可以解释维生素E、类固醇和局部麻醉样药物在肌营养不良症中的作用。由于许多已用于其他目的的临床药物可用于控制前列腺素的合成或作用,因此该假说具有直接的潜在临床应用价值。