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  • Title: Heterogeneity of nucleoside transport inhibitory sites in heart: a quantitative autoradiographical analysis.
    Author: Parkinson FE, Clanachan AS.
    Journal: Br J Pharmacol; 1989 Jun; 97(2):361-70. PubMed ID: 2788021.
    Abstract:
    1. The distribution of nucleoside transport inhibitory sites in rat and guinea-pig cardiac sections was investigated by use of [3H]-nitrobenzylthioinosine ([3H]-NBMPR) autoradiography. The distribution of these sites was heterogeneous in guinea-pig sections and homogeneous in rat sections. 2. The areas of high density of nucleoside transport inhibitory sites found in guinea-pig cardiac sections were compared to the distribution of an endothelial cell marker, von Willebrand Factor, determined by radioimmunocytochemistry. These two markers were co-localized suggesting that coronary endothelial cells from guinea-pig have a high density of NBMPR binding sites and thus may have a high nucleoside transport capacity. 3. Nucleoside transporter subtypes with differing affinity for NBMPR or dipyridamole were investigated by quantitative autoradiography. Sites in rat tissues had high affinity for NBMPR (KD = 0.6 nM) but were of low sensitivity to dipyridamole (Ki = 3.1 microM). In guinea-pig sections, areas of high and low [3H]-NBMPR binding site density were analyzed separately. In both areas, sites had high affinity for NBMPR (KD = 1.4 nM, 4.5 nM, respectively) and dipyridamole (Ki = 108 nM, 245 nM, respectively). 4. While differences in density of nucleoside transport inhibitory sites are detectable between distinct regions of the heart, subtypes differing in affinity for NBMPR or dipyridamole were not evident. Therefore, more detailed structure activity studies are required to determine if subtypes of these sites exist within a single heart.
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