Ca2+ concentration influences the hepatic extraction of bioactive human PTH-(1-34) in rats

The regulation of bioactive human parathyroid hormone [hPTH-(1-34)] hepatic extraction was studied in vitro by means of an isolated rat liver perfusion system. A standard buffer containing 20% red blood cells, 2% albumin, and variable concentrations of hPTH-(1-34) and Ca2+ was used in nonrecirculation experiments. Hepatic blood flow was kept constant at approximately 1.8 ml.g liver-1.min-1. hPTH in portal and hepatic veins was measured by a radioimmunoassay specific for hPTH-(1-34), and the results obtained were validated by gel chromatography analysis of the hormone measured. Results are expressed as mean +/- SD of five to six different experiments. In normocalcemic conditions (Ca2+ approximately 1.2 mmol/l), the hepatic extraction ratio of hPTH remained stable at 0.357 +/- 0.011 and 0.370 +/- 0.010 for hPTH-(1-34) concentrations of 0.156 +/- 0.002 and 1.314 +/- 0.014 pmol/ml; it decreased to 0.145 +/- 0.013 (P less than 0.001) for a hPTH-(1-34) concentration of 5.817 +/- 0.167 pmol/ml. Kinetics analysis of the normocalcemic data disclosed a Vmax of 1.971 +/- 0.18 pmol.min-1.g liver-1 and a Km of 1.410 +/- 0.39 pmol/ml. When hPTH-(1-34) concentration was kept stable with varying Ca2+ concentrations, elevated (1.62 +/- 0.01 mmol/l) Ca2+ gave an hepatic extraction ratio similar to normocalcemic conditions (0.335 +/- 0.014 vs. 0.357 +/- 0.011 mmol/l), whereas it significantly decreased in hypocalcemia (0.78 +/- 0.01 mmol/l) to 0.219 +/- 0.014 mmol/l (P less than 0.001). Kinetics were similar to normocalcemic conditions when Ca2+ concentration was elevated but appeared modified by hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)