85-1437-48　［取扱停止］Parathyroid Hormone, Recombinant, Human (PTH) (1-34) 500ug　P3109-27

特徴

• Polypeptide hormones secreted by the parathyroid glands, which promote release of calcium from bone to extracellular fluid by activating osteoblasts and inhibiting osteoclasts, indirectly promote increased intestinal absorption of calcium and promote renal tubular reabsorption of calcium and increased renal excretion of phosphates. It is a major regulator of bone metabolism. Secretion of parathyroid hormone increases when the level of calcium in the extracellular fluid is low. Its action is opposed by calcitonin. Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body. PTH half-life is approximately 4 minutes. PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone.
• In the kidney, PTH enhances active reabsorption of calcium and magnesium from distal tubules and the thick ascending limb. As bone is degraded both calcium and phosphate are released. It also greatly increases the excretion of phosphate, with a net loss in plasma phosphate concentration. By increasing the calcium:phosphate ratio more calcium is therefore free in the circulation. PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system. Normal total plasma calcium level ranges from 8.5 to 10.2mg/dL (2.12mmol/L to 2.55mmol/L).
• Recombinant Human PTH is a single, non-glycosylated, polypeptide chain containing 34 amino acids and having a molecular mass of 4117.8 Dalton.
• Sequence:The sequence of the first five N-terminal amino acids was determined and was found to be Ser-Val-Ser-Glu-Ile.
• Dimers and Aggregates:≤ 1% as determined by silver-stained SDS-PAGE gel analysis.
• Biological Activity:rHuPTH is fully biologically active when compared to standards. The activity calculated by UMR106 cell/cAMP method corresponding to a specific activity of 1.0 x 10e4 Units/mg.
• Endotoxin:≤ 0.1ng/ug (IEU/ug) of rHuPTH.
• Protein Content:Protein quantitation was carried out by two independent methods:1. UV spectroscopy at 280nm. 2. Analysis by RP-HPLC, using a calibrated solution of PTH as a Reference Standard.
• Reconstitution:Reconstitute the lyophilized rHuPTH in sterile 18MΩ-cm H2O not less than 100ug/ml, which can then be further diluted to other aqueous solutions.
• Storage and Stability:Lyophilized powder may be stored at 4°C for short-term only. Reconstitute to nominal volume by adding sterile dH2O and store at -20°C. Reconstituted product is stable for 12 months at -20°C. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.