(3H)dipyridamole and (3H)nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: A comparison

Deckert, Jürgen; Hennemann, A.; Bereznai, Benjámin; Fritze, Jürgen; Vock, R.; Marangos, Paul J.; Riederer, Peter

doi:10.1016/0024-3205(94)00276-2

Cited by 9 publications

(8 citation statements)

References 27 publications

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“…Furthermore, K, values for inhibition of ['HINBI binding to es' nucleoside transporters were 0.2 nM for NB!, 2.9 nM for DPR, and 0.3 nM for dilazep (Marangos, 1984) and were 1.5 nM for NBI and 5.4 nM for DPR (Deckert et al, 1993) in membranes of human brain. Similar results were obtained for inhibition of ['H1DPR binding to es nucleoside transporters in membranes of human brain; K~values were 2.6 nM for NBI and 6.5 nM for DPR (Deckert et al, 1994). Recently, a high proportion of I 3HIDPR binding sites in postmortem human ependyma was shown to be NBI insensitive (Jones-Humble and Morgan, 1994).…”

Section: Discussionsupporting

confidence: 76%

“…N3Icib transporters are concentrative NBI-insensitive and exhibit a broad selectivity to purines and pyrirnidines, and cs' transporters are concentrative and sensitive to inhibition by low nanomolar concentrations of NBI (Cass, 1995;Geiger et al, 1996). Expression of these transporters is not uniform among cell types: Whereas nonhuman tissues express to varying degrees cs, ci, and concentrative nucleoside transporters, human tissues such as human erythrocytes and postmortem human parietal cortex appear to express only cc transporters (Plagemann and Wohlhueter, 1980;Plagemann and Woffendin, 1988;Crawford et al, 1990;Deckert et al, 1994). In human ependymal tissue, however, it was reported that [ 3H] dipyridamole ([3H I DPR) binding to ci nucleoside transporters was 10 times higher than that to es sites (Jones-Humble and Morgan, 1994).…”

mentioning

confidence: 99%

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Characterization of Inhibitor‐Sensitive and ‐Resistant Adenosine Transporters in Cultured Human Fetal Astrocytes

Gu¹,

Nath

Geiger³

1996

Journal of Neurochemistry

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The kinetic characteristics of [ 3H]adenosine uptake, the extent to which accumulated [3H]adenosine was metabolized, the effects such metabolism had on measurements of apparent Michaelis-Menten kinetic values of KT and Vmnx, and the sensitivities with which nucleoside transport inhibitors blocked [3H]adenosine accumulations were determined in cultured human fetal astrocytes. KT and Vrnax values for accumulations of [3H]labeled purines using 15-s incubations in the absence of the adenosine deaminase inhibitor e,ythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and the adenosine kinase inhibitor 5'-iodotubercidin (ITU) were 6.2 1iM and 0.15 nmol/ mm/mg of protein for the high-affinity and 2.6 mM and 21 nmol/min/mg of protein for the low-affinity components, respectively. In the presence of EHNA and ITU, where <4% of accumulated [ 3H]adenosinewas metabolized, transport per se was measured, and kinetic values for KT and V~axwere 179 1iM and 5.2 nmol/min/mg of protein, respectively. In the absence of EHNA and ITU, accumulated [ 3H]adenosinewas rapidly metabolized to AMP, ADP, and ATP, and caused an appearance of "concentrative" uptake in that the intracellular levels of [3H]-labeled purines (adenosine plus its metabolites) were 1.4-fold higher than in the medium. No apparent concentrative accumulations of [3H]adenosine were found when assays were conducted using short incubation times in the absence or presence of EHNA and ITU. The nucleoside transport inhibitors dipyridamole (DPR), nitrobenzylthioinosine (NBI), and dilazep biphasically inhibited [3H}adenosine transport; for the inhibitor-sensitive components the IC 50 values were 0.7 nM for NBI, 1.3 nM for DPR, and 3.3 nM for dilazep, and for the inhibitor-resistant component the IC50 values were 2.5 1iM for NBI, 5.1 1j,M for dilazep, and 39.0 1jM for DPR. These findings, in cultured human fetal astrocytes, represent the first demonstration of inhibitor-sensitive and -resistant adenosine transporters in nontransformed human cells.

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Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 99%

Characterization of Inhibitor‐Sensitive and ‐Resistant Adenosine Transporters in Cultured Human Fetal Astrocytes

Gu¹,

Nath

Geiger³

1996

Journal of Neurochemistry

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“…These studies, which assessed the effects of dipyridamole on uridine transport by the recombinant chimeras, also eliminated involvement of(i) the large cytoplasmic loop between transmembrane domains 6 and 7 and (ii) the amino terminus up to the end of transmembrane 2 and including the large extracellular loop between transmembrane domains 1 and 2 in the inhibitory action of dipyridamole. Since dipyridamole is a competitive inhibitor of human es transport activity and NBMPR binding (Paterson et al, 1980;Jarvis et al, 1982;Jarvis, 1986;Deckert et al, 1994), it is likely that transmembrane domains 3-6 form part of the nucleoside-and NBMPR-binding site (Sundaram et al, 1998). The amino acid sequences of hENT1 and rENT1 in this region are 83% identical and 95% similar, thereby providing candidate residues for involvement in vasodilator binding.…”

Section: The Entl (Es) Subfamilymentioning

confidence: 95%

Nucleoside Transporters of Mammalian Cells

Cass

Young

Baldwin

et al. 2002

Pharmaceutical Biotechnology

121

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“…[1][2][3] It inhibits the uptake of adenosine into the erythrocytes 4,5 and enhances the vasodilator action of adenosine. 4 -10 While dipyridamole has been widely used for the measurement of coronary flow reserve in patients with coronary artery disease as well as coronary risk factors, 3 it has been reported that coronary atherosclerosis was a important potential risk factor for silent brain infarction.…”

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confidence: 99%

Effect of Intravenous Dipyridamole on Cerebral Blood Flow in Humans

Ito

Kinoshita

Tamura

et al. 1999

Stroke

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Background and Purpose-Dipyridamole increases the concentration of circulating adenosine, which is a potent vasodilator, by inhibition of uptake of adenosine into the erythrocytes, and hence produces coronary vasodilation. However, the effects of dipyridamole on cerebral circulation is not pronounced. This study investigates the effects of intravenous dipyridamole on cerebral blood flow (CBF) in humans with use of positron emission tomography (PET). Methods-In each of 13 healthy subjects, CBF was measured using 15 O-labeled water and PET at rest and during hypercapnia, hypocapnia, and dipyridamole stress; corresponding CBF values were then compared. Results-CBF values during dipyridamole stress were significantly lower than those measured at rest. The dipyridamole stress PaCO 2 was also significantly lower than the resting PaCO 2 . The change in CBF during dipyridamole stress relative to PaCO 2 closely followed the relationship between CBF and PaCO 2 during hypocapnia. Conclusions-These results indicate that the observed decrease in CBF during dipyridamole stress was caused by a decrease in PaCO 2 rather than by any direct action of dipyridamole on CBF. The decrease in PaCO 2 during dipyridamole stress was most likely due to hyperventilation, which was a side effect of adenosine. These results support the hypothesis that circulating adenosine is largely prevented from binding to adenosine receptors of cerebral vessels by the blood-brain barrier. (Stroke. 1999;30:1616-1620.)

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(3H)dipyridamole and (3H)nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: A comparison

Cited by 9 publications

References 27 publications

Characterization of Inhibitor‐Sensitive and ‐Resistant Adenosine Transporters in Cultured Human Fetal Astrocytes

Characterization of Inhibitor‐Sensitive and ‐Resistant Adenosine Transporters in Cultured Human Fetal Astrocytes

Nucleoside Transporters of Mammalian Cells

Effect of Intravenous Dipyridamole on Cerebral Blood Flow in Humans

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