Metabolism of parathyroid hormone in isolated perfused rat kidney and liver combined

Metabolism of synthetic, intact, human parathyroid hormone (PTH) 10(-9) M was studied in a new experimental model using the isolated perfused rat kidney and liver combined. The combined organs cleared intact PTH significantly faster than the single kidneys (P less than 0.02) or livers (P less than 0.02), but not faster than the sum of the clearances in the single organs. The kidneys cleared intact PTH without accumulation of NH2-terminal, mid-molecule or COOH-terminal iPTH, and high-performance liquid chromatography (HPLC) studies did not reveal any PTH fragments. The livers cleared mid-molecule and COOH-terminal iPTH significantly slower (P less than 0.002) than intact PTH, and HPLC demonstrated generation of mid-molecule and COOH-terminal PTH fragments. The combined organs accumulated significantly less mid-molecule (P less than 0.001) and COOH-terminal (P less than 0.03) iPTH than the single livers, and HPLC demonstrated mid-molecule peaks that were smaller but not qualitatively different. In conclusion, the predominance of COOH-terminal PTH fragments in plasma may be maintained by differential clearance mainly in the liver, excessive accumulation being prevented by filtration in the kidneys.