This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, K.-H. Articles by Cha, S. Search for Related Content PubMed PubMed Citation Articles by Lee, K.-H. Articles by Cha, S.

Inhibition of Nucleoside Transport in Murine Lymphoma L5178Y Cells and Human Erythrocytes by the Uridine Phosphorylase Inhibitors 5-Benzylacyclouridine and 5-Benzyloxybenzylacyclouridine¹

Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912

The uridine phosphorylase inhibitors, 5-benzylacyclouridine (BAU) and 5-benzyloxybenzylacyclouridine (BBAU) (Biochem. Pharmacol., 31: 1857, 1982), inhibited uptake of uridine in L5178Y cells. By a rapid sampling technique, BAU and BBAU were shown to inhibit the transport (zero-trans influx) of uridine, thymidine, and adenosine in human erythrocytes as well as in murine L5178Y cells. In all cases, competitive inhibitions were observed. K_m values for the transport of adenosine, uridine, and thymidine in erythrocytes were 2.2, 195, and 199 µM, while V_max were 2.9, 118, and 96.5 pmol/min/10⁶ cells, respectively. In L5178Y cells, K_m values of 14.8 and 23.1 µM and V_max of 389 and 176 pmol/min/10⁶ cells were obtained for adenosine and uridine, respectively. For erythrocytes, the K_i values of BAU were 127, 124, and 198 µM using adenosine, uridine, and thymidine as the substrate; and those of BBAU, 14.1 and 19.2 µM for adenosine and uridine, respectively. In L5178Y, the K_i values of BAU were 202 and 234 µM, and those of BBAU, 39.8 and 27.9 µM for adenosine and uridine, respectively. These data indicate that, in two cell types, K_i values for BAU and BBAU did not vary regardless of the substrate used; that the values of K_i are different for the erythrocytes and L5178Y cells; and that BBAU is at least 5-fold more potent than BAU as an inhibitor of nucleoside transport. The inhibitory effects on the efflux of preloaded uridine indicate that BAU and BBAU are inhibitors, rather than permeants, of the nucleoside transport system.

¹ Supported by Grant CH-136 awarded by the American Cancer Society and by Grants CA-13943 and CA-31650 awarded by the National Cancer Institute, Department of Health and Human Services.

² Recipient of support from the training program in cancer research, USPHS Grant CA 09204, awarded by the National Cancer Institute, Department of Health and Human Services.

³ To whom requests for reprints should be addressed.

Received 8/30/83. Accepted 5/23/84.