Effect of parathyroid hormone on energy metabolism of skeletal muscle.
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.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D008931:Mitochondria, Muscle / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019379:Teriparatide; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D010725:Phosphocreatine; D019379:Teriparatide; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014700:Verapamil; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases