Evidence of two forms of hepatic extraction of parathyroid hormone in dogs in vivo

The fractional hepatic extraction (FHE) of oxidized 125iodine-labeled bovine parathyroid hormone, 125I-bPTH-(1-84), is dependent on the integrity of the 28-48 sequence of the bPTH structure. A second type of FHE, related to the biologically active core of the hormone, is suggested by liver adenylate cyclase activation or cAMP production by bPTH-(1-84) or bPTH-(1-34). We have thus compared the FHE of biologically active bPTH-(1-84), bPTH-(1-34), and of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide with that of oxidized 125I-bPTH-(1-84). The preparations, together with reference substances, were injected into the portal vein of anesthetized dogs and dilution curves obtained by counting the radioactivity or assaying the immunoreactivity present in hepatic vein samples. FHE was calculated from these curves. Results were validated by gel chromatography analysis of the 125I-radioactive or immunoreactive preparation injected and recovered. In six dogs, the FHE of bPTH-(1-84) was 59.9 +/- 8.9%, 23% higher than the value of 39.6 +/- 9.3% obtained for 125I-bPTH-(1-84) injected simultaneously (P less than 0.0005). This difference was similar to the FHE of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide (16.4 +/- 7.2%) and bPTH-(1-34) (23.5 +/- 10.4%) measured in seven dogs. Analysis of the various gel chromatography profiles revealed that the entire FHE process could be explained by extraction of the appropriate peak of each preparation; a small amount of fragment was also generated across the liver in the case of bPTH-(1-84) (1.6%) and 125I-[Nle8, Nle18, Tyr34]-bPTH-(1-34) amide (2.8%), with a larger quantity in the case of bPTH-(1-34) (17%).(ABSTRACT TRUNCATED AT 250 WORDS)