Acute lithium administration impairs the action of parathyroid hormone on rat renal calcium, magnesium and phosphate transport.
1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown. 2. The present study evaluated the acute effect of Li+ on renal electrolyte transport, particularly Ca2+ and Mg2+ in thyroparathyroidectomized (TPTX) and intact rats. 3. The acute administration of Li+ significantly increased water, sodium, potassium and phosphate excretion in both TPTX and intact animals; however, Ca2+ and Mg2+ excretion was only increased in the intact group. Fractional excretion (FE) of Ca2+ and Mg2+ increased from 2.2 +/- 0.2 to 3.5 +/- 0.3% and 12 +/- 2 to 18 +/- 2%, respectively (P < 0.01). 4. In further experiments in TPTX rats, Li+ administration inhibited the usual reduction in urine Ca2+ and Mg2+ excretion following parathyroid hormone (PTH) administration and inhibited the phosphaturia. However, supramaximal concentrations of PTH overcame this inhibitory effect. For example, an FECa of 3.8 +/- 0.2% was reduced to 1.4 +/- 0.2% and 1.7 +/- 0.2% with maximal and supramaximal PTH concentrations, respectively, while in the presence of Li+ an FECa of 4.0 +/- 0.2 was decreased to 2.8 +/- 0.2 and then 1.9 +/- 0.3% with the same PTH concentrations. 5. The inhibitory effect of Li+ was reduced with a lower plasma Li+ concentration (0.7 +/- 0.2 vs 1.6-1.8 mmol/L). The FEMg results were comparable. 6. These results demonstrate that Li+ directly inhibits PTH-mediated renal reabsorption of Ca2+ and Mg2+ and also blunts PTH-mediated phosphaturia. Therefore, the hyperparathyroidism in humans following Li+ treatment may be a consequence of reduced renal Ca2+ reabsorption.
Faculty of Medicine & Health Sciences, University of Newcastle, New South Wales, Australia.
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Carney
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Jackson
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D016105:Parathyroidectomy; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014867:Water / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D014867:Water; D008094:Lithium; D008274:Magnesium; D002118:Calcium