AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E87-E92, Copyright © 1989 by American Physiological Society
Ca2+ concentration influences the hepatic extraction of bioactive human PTH-(1-34) in rats
P. D'Amour and P. M. Huet
Centre de Recherche Clinique Andre-Viallet, Hopital Saint-Luc, Montreal, Quebec, Canada.
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)
