It is known that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] mobilizes inorganic phosphate (Pi) from gut and bone, thus increasing the entry of Pi into the extracellular space (ECS). In this work, we have investigated whether 1,25(OH)2D3 could also facilitate the net exit of Pi out of this pool into certain soft tissue and/or bone compartments in thyroparathyroidectomized (TPTX) rats. Sham-operated, TPTX, and TPTX rats treated with 1,25(OH)2D3 (26 pmol/day ip for 1 wk) were infused with a known amount of Pi over a given time. The amount of Pi excreted in the urine in excess of base-line values and the rise of the phosphatemia ([Pi]p) were measured. The difference between these two parameters corresponded to the net retention of infused Pi in the whole animal (RAPi) for a given rise in [Pi]p. The results show that RAPi was markedly diminished in TPTX as compared with sham-operated animals. This decrease could be corrected by 1,25(OH)2D3 treatment. Chronic reduction in the level of calcemia in TPTX 1,25(OH)2D3-supplemented rats as induced by decreasing dietary Ca intake also diminished RAPi. These effects could not be ascribed to the known actions of the experimental maneuvers on the renal excretion of Pi. Since infusions were chosen to obtain similar rises in [Pi]p and started from same levels of [Pi]p in animals of the same weight, the differences in RAPi were not due to variation of Pi retention in the ECS.(ABSTRACT TRUNCATED AT 250 WORDS)
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http://dx.doi.org/10.1152/ajprenal.1985.249.6.F912 | DOI Listing |
JBMR Plus
June 2024
Extend Biosciences, Inc., Newton, MA 02458, United States.
Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP).
View Article and Find Full Text PDFJBMR Plus
July 2020
Research Division Chugai Pharmaceutical Co., Ltd Shizuoka Japan.
Prolonged signaling at the parathyroid hormone receptor 1 (PTHR1) correlates with the capacity of a ligand to bind to a G protein-independent receptor conformation (R). As long-acting PTH (LA-PTH) ligands hold interest as potential treatments for hypoparathyroidism (HP), we explored the structural basis in the ligand for stable R binding and prolonged cAMP signaling. A series of PTH/PTHrP hybrid analogs were synthesized and tested for actions in vitro and in vivo.
View Article and Find Full Text PDFClin Kidney J
October 2019
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Background: Parathyroidectomy (PTX) that alleviates clinical manifestations of advanced hyperparathyroidism, including hypercalcemia and hypophosphatemia, is considered the best protection from calcium overload in the kidney. However, little is known about the relationship between postsurgical robust parathyroid hormone (PTH) reduction and perisurgical renal tubular cell viability. Post-PTX kidney function is still a crucial issue for primary hyperparathyroidism (PHPT) and tertiary hyperparathyroidism after kidney transplantation (THPT).
View Article and Find Full Text PDFExp Anim
October 2017
Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai 200240, P.R. China.
Parathyroidectomy (PTX), especially total parathyroidectomy (TPTX), is often recommended for severe secondary hyperparathyroidism (SHPT) if other medical treatments fail. Accurate identification and resection of parathyroid gland (PTG) tissue is the cornerstone of PTX. The establishment of a rat TPTX model would be beneficial for several applications but faces the same problems.
View Article and Find Full Text PDFJ Bone Miner Res
July 2016
Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Hypoparathyroidism is a disease of chronic hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone (PTH). PTH and analogs of the hormone are of interest as potential therapies. Accordingly, we examined the pharmacological properties of a long-acting PTH analog, [Ala(1,3,12,18,22) , Gln(10) ,Arg(11) ,Trp(14) ,Lys(26) ]-PTH(1-14)/PTHrP(15-36) (LA-PTH) in thyroparathyroidectomized (TPTX) rats, a model of HP, as well as in normal monkeys.
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