Membrane Transport of Purines and Pyrimidines in a Cestode

Abstract

Experiments indicate that the rat cestode Hymenolepis diminuta possesses at least one locus for the mediated transport of purines and pyrimidines. Hypoxanthine has the greatest affinity for the locus as evidenced by its rate of uptake and activity as an inhibitor. Uracil and adenine have a mediated transport at low concentrations. Thymine and cytosine apparently enter mainly by diffusion. Reciprocal competitive inhibitions of purines and pyrimidines were observed. Thymine competitively stimulated uracil transport. Kinetic data on uptake and inhibition of uptake are presented. The purine-pyrimidine transport locus is distinct from the loci for sugar and amino acid transport already known for this organism. Considerable evidence has accumulated indicating that organisms utilize exogenously supplied purine and pyrimidine bases for synthesis of nucleic acids or other cell components (Brown, 1953; Bolton and Reynard, 1954; Cowie and Bolton, 1957; Henderson, 1962; Wilson and Wilson, 1958, 1962; and others). The mode of passage of these compounds into or out of cells appears to vary with the organism studied. Simple diffusion may be the only entry process involved for a given compound in some organisms, whereas mediated processes may be partially or wholly responsible for the transport of the same compound in other cases. Wilson and Wilson (1958) reported that pyrimidines were not actively transported by rat gut, but later studies by Shanker and Tocco (1960, 1962) and Shanker and Jeffrey (1961) showed that mediated transport was evident at low concentrations of pyrimidines. These authors demonstrated that absorption of pyrimidines by rat, frog, and hamster gut consisted of two processes, diffusion and mediated transport. The mediated transport was inhibited by pyrimidines and by hypoxanthine. The site for pyrimidine active transport was distinct Received for publication 12 November 1964. * This work was supported by grants from the National Institutes of Health, U. S. Public Health Service (AI 01384 and 5 Tl AI 106). The authors express gratitude for the technical assistance of Mr. W. Kitzman and Mrs. E. Hake. t NIH Postdoctoral Fellow. from the sites for transport of sugars and amino acids. McCarthy and Britten (1962) suggested mediated transport for uracil entry into Escherichia coli. Ehrlich ascites tumor cells, however, may acquire pyrimidines only by diffusion (Jacquez, 1962). A clear experimental indication for a mediated process in resorption of uric acid in normal canine kidney tubules, except in Dalmatian dogs, was provided by Friedman and Byers (1948). Harvey and Christensen (1964) confirmed the lack of a mediated transport system for uric acid in the Dalmatian. Uric acid was reported to be actively transported by human red blood cells, and this transport was inhibited by hypoxanthine (Overgaard-Hansen and Lassen, 1959). In further investigations of uric acid transport into human red blood cells, Lassen and Overgaard-Hansen demonstrated that there was both a diffusion and a mediated component of uric acid entry, and that the system also transported adenine and hypoxanthine; reciprocal inhibitions were shown with these compounds (Lassen, 1961, 1962; Lassen and Overgaard-Hansen, 1962a, b). Christensen and Jones (1961) were able to show inhibitions of hypoxanthine by purine in this same system, and Whittam (1960) reported a high permeability of human red blood cells to adenine and hypoxanthine. The Ehrlich ascites cell was reported to take up adenine only by diffusion (Ellis and Scholefield, 1962; Jacquez and Ginsberg, 1960). Roush and Shieh (1962) reported