Baczynski R, Massry S G, Magott M, el-Belbessi S, Kohan R, Brautbar N
Kidney Int. 1985 Nov;28(5):722-7. doi: 10.1038/ki.1985.190.
Clinical states with primary or secondary hyperparathyroidism are associated with muscle dysfunction, suggesting that parathyroid hormone (PTH) may affect muscle metabolism. The present study examined the effect of 1-84 PTH and its amino-terminal fragment (1-34 PTH) on energy production, transfer, and utilization by skeletal muscle. Rats weighing 150 to 200 g were injected intraperitoneally with 1-84 or 1-34 PTH, 200 U/day, for 4 days, and control animals received vehicle only. The effect of the simultaneous administration of a calcium channel blocker, verapamil, was examined also. The muscle content of inorganic phosphorus, creatine phosphate, and adenine nucleotides were significantly (P less than 0.01) lower in the PTH-treated rats than in control animals. The hormone significantly reduced mitochondrial oxygen consumption without altering ADP:0 ratio, indicating reduced phosphorylation. Both 1-84 and 1-34 PTH produced significant (P less than 0.01) reduction in the activities of mitochondrial and myofibrillar CPK, and mitochondrial MgATPase. 1-84 PTH reduced the activity of myofibrillar CaATPase as well. There was a significant (P less than 0.01) increment in muscle uptake of 45Ca in the 1-84 PTH-treated rats. Verapamil abolished all the effects of PTH. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements may, at least in part, underlie the myopathy observed in conditions associated with excess PTH.
原发性或继发性甲状旁腺功能亢进的临床状态与肌肉功能障碍相关，提示甲状旁腺激素（PTH）可能影响肌肉代谢。本研究检测了1-84 PTH及其氨基末端片段（1-34 PTH）对骨骼肌能量产生、转移和利用的影响。给体重150至200 g的大鼠腹腔注射1-84或1-34 PTH，200 U/天，共4天，对照动物仅给予赋形剂。还检测了同时给予钙通道阻滞剂维拉帕米的效果。PTH处理的大鼠肌肉中无机磷、磷酸肌酸和腺嘌呤核苷酸的含量显著（P<0.01）低于对照动物。该激素显著降低线粒体氧消耗，但不改变ADP:O比值，表明磷酸化减少。1-84和1-34 PTH均显著（P<0.01）降低线粒体和肌原纤维CPK以及线粒体MgATPase的活性。1-84 PTH也降低了肌原纤维CaATPase的活性。在1-84 PTH处理的大鼠中，肌肉对45Ca的摄取显著（P<0.01）增加。维拉帕米消除了PTH的所有作用。我们的数据表明，1-84和1-34 PTH均损害能量产生、转移和利用。这些生化紊乱可能至少部分是与PTH过量相关疾病中观察到的肌病的基础。
