Characteristics of bovine parathyroid hormone extraction by dog liver in vivo.

The metabolic fate of various 125I-labeled preparations of bovine parathyroid hormone (bPTH) during a single passage through the liver was studied in anesthetized dogs. Each 125I-bPTH preparation was injected in the portal vein with 131I-albumin and 99mTc-erythrocytes, two reference indicators. A dilution curve was obtained for each indicator by counting the radioactivity present in tubes collected by hepatic vein sampling. Hepatic blood flow (HBF) and fractional hepatic extraction (FHE) were calculated from these curves. Extraction results were further validated by comparing the gel chromotography profile of the 125I injected and of the 125I recovered. The FHE of 125I after an injection of 125I-bPTH-(1--84) was 32.75 +/- 9.39% (mean +/- SD; n = 23) for a mean HBF of 48.18 +/- 11.83 ml . kg-1 . min-1. The FHE was independent of the dose of hormone injected (0.34-812 ng) but was inversely related to the HBF (r = -0.6768, P less than 0.001). 125I was not extracted after an injection of 125I-bPTH-(1--34) ( n = 8) or of 125I-bPTH-(34/43--84) (n = 5). On the other hand, after an injection of 125I-bPTH-(28--48), 18.7 +/- 5.5% (n = 8) of the 125I was extracted for an HBF of 47.3 +/- 17.0 ml . kg-1 . min-1. Analysis of the gel chromotography profiles further disclosed that 7.6 +/- 4.2% of the 125I-bPTH-(1--84) injected was transformed into carboxyl terminal fragments; 13.1 +/- 2.6% of the 125I-bPTH-(28--48) and 20.9 +/- 4.9% of the 125I-bPTH-(1--34) injected were also cleaved into smaller molecular weight products. We conclude that the integrity of the sequence 28--48 is important for the FHE of 125I-bPTH-(1--84). Although nonsaturable, this process is inversely related to the HBF. Liver inactivation of intact PTH or of its fragments also proceeds through rapid cleavage into smaller molecular weight products.