NUCLEOSIDE TRANSPORT AND METABOLISM IN HUMAN IMMUNE CELLS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

NUCLEOSIDE TRANSPORT AND METABOLISM IN HUMAN IMMUNE CELLS (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2355 1992. Unique Identifier : AIDSLINE ICDB/92685077
Chan TC; Shaffer L; Redmond R; Pennington KL; Dept. of Physiology and Pharmacology, Purdue Univ., W. Lafayette,; IN 47907

Abstract: There is a broad-specificity nucleoside transporter on mammalian cell membranes which is responsible for the facilitated uptake of endogenous nucleosides. It is unclear whether this nucleoside transport system is present in human immune cells, and whether any of the anti-HIV dideoxynucleosides are substrates of this facilitated uptake system. We have studied nucleoside permeation and metabolism in lymphocytes, macrophages, and bone marrow mononuclear cells isolated from healthy human volunteers and found a saturable zero-trans nucleoside transport system in each of the three cell types. Of the five dideoxynucleoside analogs tested (AZT, DDC, DDI, DDA and DDT), not one is a substrate for this nucleoside transport system. Long periods of equilibration (1-2 hr) resulted in low levels (by passive diffusion) of DDA and AZT, but undetectable levels of DDC, DDI and DDT inside the immune cells. Only the phosphates of AZT and DDA reached detectible levels in the perchloric acid extracts of lymphocytes after 24 hr of incubation. Our data suggest that the ability of anti-HIV dideoxynucleosides to permeate immune cells is an important issue in new drug development.

Keywords: Biological Transport Bone Marrow/METABOLISM Dideoxynucleosides/*METABOLISM Drug Design Human Kinetics Lymphocytes/*METABOLISM Macrophages/*METABOLISM Monocytes/*METABOLISM Nucleosides/*METABOLISM ABSTRACT
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M9281090

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