METABOLISM OF N-TERMINAL AND C-TERMINAL PARATHYROID-HORMONE FRAGMENTSBY ISOLATED-PERFUSED RAT-KIDNEY AND LIVER

The metabolism of added N-terminal and C-terminal synthetic human PTH (synhPTH) fragments was studied in isolated perfused rat livers and in filtering and nonfiltering kidneys. Initial concentrations: synhPTH-( 1-34), 14 pmol/liter, synhPTH-(39-84) 85 pmol/liter, synhPTH-(1-84) 3 pmol/liter, or 1000 pmol/liter of each fragment and intact PTH. Cleara nces were measured by assays specific for intact PTH, N-terminal, midm olecule, and C-terminal immunoreactive PTH. Metabolism of the added PT H into smaller circulating fragments was analyzed by HPLC. The clearan ce of synhPTH-(1-34) in the filtering kidneys was not significantly di fferent from the clearance of synhPTH(39-84) and inulin, and HPLC demo nstrated no metabolism of synhPTH-(1-34) or synhPTH-(39-84) in the kid neys. The livers did not clear synhPTH-(39-84), while the clearance of synhPTH-(1-34) was significant (P < 0.005). HPLC demonstrated no meta bolism of synhPTH-(39-84) by the livers, but extensive metabolism of s ynhPTH(1-34). The livers cleared synhPTH-(1-34) significantly (P < 0.0 5) faster than synhPTH-(1-84). In conclusion, the kidneys cleared N-te rminal PTH fragments at the same rate as C-terminal fragments mainly b y filtration. The livers cleared N-terminal fragments faster than inta ct PTH, but did not clear C-terminal fragments. This differential hepa tic clearance may play a major role in maintaining the differences bet ween the circulating levels of N-terminal and C-terminal immunoreactiv e PTH.