Distinct regional distribution of human equilibrative nucleoside transporter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system

Nucleoside transport processes play an important role in human cells in sal vage of nucleosides used in the biosynthesis of nucleic acids and in regula ting endogenous adenosine concentrations in the human central nervous syste m (CNS). By altering the levels of adenosine available to interact with cel l-surface receptors, nucleoside transporters have profound effects on the a bility of adenosine to modulate neurotransmission, vascular tone and other physiological events. Although the human equilibrative nucleoside transport ers 1 and 2 (hENT1 and hENT2) are believed to play a crucial role in modula ting brain function, their distribution within the major divisions of the h uman CNS is not known. In this work, antibodies specific for hENT1 and hENT 2 were produced against fragments of the transporter proteins and used for immunoblot analysis of enriched membrane fractions prepared from several re gions of the human brain. While hENT1 was most prevalent in the frontal and parietal lobes of the cerebral cortex, thalamus, midbrain and basal gangli a, hENT2 was concentrated in the cerebellum and brainstem regions, particul arly the pens. The apparent reciprocal distribution of hENT1 and hENT2 in h uman brain suggests that these nucleoside transporter proteins are produced in distinct regions of the CNS where they function in nucleoside salvage a nd/or regulation of exogenous adenosine. Within the brain regions that were investigated, the pattern of hENT1 distribution correlated well with adeno sine A(1) receptor abundance. The regional co-localization of hENT1 and A(1 ) receptor protein suggests an important role of hENT1-mediated transport p rocess in the control of neuromodulatory actions mediated by adenosine A, r eceptors in human brain. (C) 2001 Elsevier Science Ltd. All rights reserved .