The sources of bile pigment in the rat: studies of the "early labeled" fraction.

Abstract

Formation of labeled hemoglobin-heme and bilirubin was studied in rats, using glyclne 2-C14 or delta-am inolevulinic acid-4-C14 as precursors. Two experimental models were used: the congenitally icteric Gunn rat In which labeled bilirubin formation was computed from the sequential changes In plasma bilirubin specific activity; and normal rats with external bile fistulas, In which labeled pigment excretion was measured in the bile. Similar results were obtained with both models. After C14-giycine about 84% of the total C14 bilirubin produced was derived from random and senescent loss of circulating red cells. The early labeled peak (ELP) comprised 16% of the total and was maximal at 1-2 hr. The Initial component between 0 and 3 1/2 hr. was totally independent of erythropoiesis. Similarly, the later component from 3 1/2 to 60 hr. was largely unaffected by erythroid suppression, but did contain a small erythropoietic component which became significant only with erythroid stimulation. This increase with erythroid stimulation was proportionate to the increase in late bile pigment formation from circulating hemoglobin, i. e. the ELP remained 13% of the total labeled pigment produced. With delta-aminolevulinic acid as precursor, the initial ELP component was magnified 1000-fold, whereas labeling of hemoglobin-heme was diminished. As a result, the ELP comprised the major fraction of the total labeled pigment produced from this precursor. These experiments indicate that in rats under normal conditions the ELP is derived almost entirely from non-hemoglobin sources, and that these sources are preferentially labeled by delta-aminolevulinic acid.