Metabolism of Radioiodinated Carboxy-Terminal Fragments of Bovine Parathyroid Hormone in Normal and Anephric Rats*

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Abstract
[125I]Carboxy-terminal fragments were produced by incubating [125I]bovine PTH(1-84) with plasma membranes from the rat renal cortex. After purification by gel chromatography and characterization by sequence analysis, these fragments, mainly [125I]bovine PTH(41-84) were injected into normal and acutely nephrectomized rats during 2 different experiments. In each case, blood was obtained from 5 rats at various time points (2, 4, 6, 8, 12, 24, 48 and 96 min); tissue was taken after they had been killed (4, 8, 24 and 96 min). Plasma and weighted aliquots of tissues were counted. Plasma at each time point and the extract of various tissues at the 8 min mark were further analyzed by gel chromatography. Each radioactivity peak on each profile was identified and quantitated planimetrically. [125I]Carboxy-terminal fragments were extracted from serum biexponentially; the 1st exponential had a half-life of 2.3 min and the 2nd 27.2 min in normal rats. These values increased in 3.2 min (x 1.4) and 74.0 min (x 2.7) in nephrectomized rats. In normal rats, 125I-extraction was 33.4% (kidney), 15.9% (muscle), 6.9% (bone), less than 2.7% (liver) and under 1% in other tissues. In nephrectomized rats, these values were significantly (P < 0.005) increased to 24.6% (muscle), 10% (bone), and 6.8% (liver) with less than 1% in other tissues. Most of the 125I-radioactivity present in these tissues at the 8-min time point migrated in the same manner as injected fragments or smaller degradation products generated in situ. Tissues which play a secondary role in circulating carboxy-terminal fragment extraction in normal rats can therefore increase this activity in anephric animals. Extraction overall remains less efficient, as demonstrated by the longer half-life of fragments in nephrectomized rats.