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Anaclet Ngezahayo - One of the best experts on this subject based on the ideXlab platform.

  • Dipyridamole related enhancement of gap junction coupling in the gm 7373 aortic endothelial cells correlates with an increase in the amount of connexin 43 mrna and protein as well as gap junction plaques
    Journal of Bioenergetics and Biomembranes, 2013
    Co-Authors: Daniela Begandt, Almke Bader, Lutz Dreyer, Anaclet Ngezahayo, Linda Gerhard, Julia Lindner, Barbara Schlingmann
    Abstract:

    Previous data showed that Dipyridamole enhanced gap junction coupling in vascular endothelial and smooth muscle cell lines by a cAMP-dependent mechanism. The present study investigates the level at which Dipyridamole affects gap junction coupling. In the GM-7373 endothelial cell line, scrape loading/dye transfer experiments revealed a rapid increase in gap junction coupling induced during the first 6 h of Dipyridamole treatment, followed by a slow increase induced by further incubation. Immunostaining analyses showed that the rapid enhancement of gap junction coupling correlated with an increased amount of Cx43 gap junction plaques and a reduced amount of Cx43 containing vesicles, while the amount of Cx43 mRNA or protein was not changed during this period, as found by semiquantitative RT-PCR and Western blot. Additionally, brefeldin A did not block this short-term-induced enhancement of gap junction coupling. Along with the Dipyridamole-induced long-term enhancement of gap junction coupling, the amount of Cx43 mRNA and protein additionally to the amount of Cx43 gap junction plaques were increased. Furthermore, the anti-Cx43 antibody detected only two bands at 42 kDa and 44 kDa in control cells and cells treated with Dipyridamole for 6 h, while long-term Dipyridamole-treated cells showed a third band at 46 kDa. We propose that a Dipyridamole-induced cAMP synthesis increased gap junction coupling in the GM-7373 endothelial cell line at different levels: the short-term effect is related to already oligomerised connexins beyond the Golgi apparatus and the long-term effect involves new expression and synthesis as well as posttranslational modification of Cx43.

  • Biphasic increase of gap junction coupling induced by Dipyridamole in the rat aortic A-10 vascular smooth muscle cell line
    Journal of Cell Communication and Signaling, 2013
    Co-Authors: Daniela Begandt, Almke Bader, Lutz Dreyer, Natalie Eisert, Thilo Reeck, Anaclet Ngezahayo
    Abstract:

    The rat aortic smooth muscle cell line A-10 was used to investigate the effect of Dipyridamole on the gap junction coupling of smooth muscle cells. The scrape loading/dye transfer (SL/DT) technique revealed that Dipyridamole concentrations between 5 μM and 100 μM significantly increased gap junction coupling. The adenosine receptor antagonist MRS 1754, as well as the PKA inhibitors Rp-cAMPS and H-89 were able to inhibit the Dipyridamole-related increase in coupling, while forskolin and Br-cAMP also induced an enhancement of the gap junction coupling. Regarding the time-dependent behaviour of Dipyridamole, a short-term effect characterised by an oscillatory reaction was observed for application times of less than 5 h, while applications times of at least 6 h resulted in a long-term effect, characterised by a constant increase of gap junction coupling to its maximum levels. This increase was not altered by prolonged presence of Dipyridamole. In parallel, a short application of Dipyridamole for at least 15 min was found to be sufficient to evoke the long-term effect measured 6 h after drug washout. We propose that in both the short-term and long-term effect, cAMP-related pathways are activated. The short-term phase could be related to an oscillatory cAMP effect, which might directly affect connexin trafficking, assembly and/or gap junction gating. The long-term effect is most likely related to the new expression and synthesis of connexins. With previous data from a bovine aortic endothelial cell line, the present results show that gap junction coupling of vascular cells is a target for Dipyridamole.

Hanschristoph Diener - One of the best experts on this subject based on the ideXlab platform.

  • early treatment with aspirin plus extended release Dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset early trial a randomised open label blinded endpoint trial
    Lancet Neurology, 2010
    Co-Authors: Reinhard Dengler, Hanschristoph Diener, A Schwartz, Martin Grond, Helmut Schumacher, Thomas Machnig, Christoph C Eschenfelder, Joachim Leonard, Karin Weissenborn, Andreas Kastrup
    Abstract:

    Summary Background Little is known about the best antiplatelet treatment immediately after ischaemic stroke or transient ischaemic attack (TIA). The EARLY trial aimed to compare outcome in patients given aspirin plus extended-release Dipyridamole twice daily either within 24 h of stroke or TIA or after 7 days of aspirin monotherapy. Methods In 46 stroke units in Germany, patients aged 18 years or more who presented with symptoms of an acute ischaemic stroke that caused a measurable neurological deficit (National Institutes of Health stroke scale score ≤20) were randomly assigned to receive 25 mg aspirin plus 200 mg extended-release Dipyridamole open-label twice daily or 100 mg aspirin monotherapy open-label once daily for 7 days. Patients were randomised by use of a pseudorandom number generator. All patients were then given open-label aspirin plus extended-release Dipyridamole for up to 90 days. The primary endpoint was modified Rankin scale score as recorded by centralised, blinded assessment by telephone (tele-mRS) at 90 days. Vascular adverse events (non-fatal stroke, TIA, non-fatal myocardial infarction, and major bleeding complications) and mortality were assessed in a composite safety and efficacy endpoint. Patients were analysed as treated. This trial is registered, number NCT00562588. Findings Between July, 2007, and February, 2009, 543 patients were treated: 283 received early aspirin plus extended-release Dipyridamole and 260 received aspirin plus extended-release Dipyridamole after 7 days on aspirin. At day 90, 154 (56%) patients in the aspirin plus early extended-release Dipyridamole group and 133 (52%) in the aspirin plus later extended-release Dipyridamole group had no or mild disability (tele-mRS 0 or 1; difference 4·1%, 95% CI −4·5 to 12·6, p=0·45). 28 patients in the early initiation group and 38 in the late initiation group reached the composite endpoint (hazard ratio 0·73, 95% CI 0·44–1·19 p=0·20). Interpretation Early initiation of aspirin plus extended-release Dipyridamole within 24 h of stroke onset is likely to be as safe and effective in preventing disability as is later initiation after 7 days. Funding Boehringer Ingelheim.

  • early treatment with aspirin plus extended release Dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset early trial a randomised open label blinded endpoint trial
    Lancet Neurology, 2010
    Co-Authors: Reinhard Dengler, Hanschristoph Diener, A Schwartz, Martin Grond, Helmut Schumacher, Thomas Machnig, Christoph C Eschenfelder, Joachim Leonard, Karin Weissenborn
    Abstract:

    Summary Background Little is known about the best antiplatelet treatment immediately after ischaemic stroke or transient ischaemic attack (TIA). The EARLY trial aimed to compare outcome in patients given aspirin plus extended-release Dipyridamole twice daily either within 24 h of stroke or TIA or after 7 days of aspirin monotherapy. Methods In 46 stroke units in Germany, patients aged 18 years or more who presented with symptoms of an acute ischaemic stroke that caused a measurable neurological deficit (National Institutes of Health stroke scale score ≤20) were randomly assigned to receive 25 mg aspirin plus 200 mg extended-release Dipyridamole open-label twice daily or 100 mg aspirin monotherapy open-label once daily for 7 days. Patients were randomised by use of a pseudorandom number generator. All patients were then given open-label aspirin plus extended-release Dipyridamole for up to 90 days. The primary endpoint was modified Rankin scale score as recorded by centralised, blinded assessment by telephone (tele-mRS) at 90 days. Vascular adverse events (non-fatal stroke, TIA, non-fatal myocardial infarction, and major bleeding complications) and mortality were assessed in a composite safety and efficacy endpoint. Patients were analysed as treated. This trial is registered, number NCT00562588. Findings Between July, 2007, and February, 2009, 543 patients were treated: 283 received early aspirin plus extended-release Dipyridamole and 260 received aspirin plus extended-release Dipyridamole after 7 days on aspirin. At day 90, 154 (56%) patients in the aspirin plus early extended-release Dipyridamole group and 133 (52%) in the aspirin plus later extended-release Dipyridamole group had no or mild disability (tele-mRS 0 or 1; difference 4·1%, 95% CI −4·5 to 12·6, p=0·45). 28 patients in the early initiation group and 38 in the late initiation group reached the composite endpoint (hazard ratio 0·73, 95% CI 0·44–1·19 p=0·20). Interpretation Early initiation of aspirin plus extended-release Dipyridamole within 24 h of stroke onset is likely to be as safe and effective in preventing disability as is later initiation after 7 days. Funding Boehringer Ingelheim.

  • efficacy of aspirin plus extended release Dipyridamole in preventing recurrent stroke in high risk populations
    JAMA Neurology, 2005
    Co-Authors: Ralph L Sacco, Juhani Sivenius, Hanschristoph Diener
    Abstract:

    Objective To assess the efficacy of aspirin plus extended-release Dipyridamole compared with aspirin alone for the prevention of recurrent stroke among high-risk groups. Design A post hoc analysis was conducted using data from the European Stroke Prevention Study 2. Rates of annual strokes and vascular events were determined for the aspirin plus extended-release Dipyridamole group (n = 1650) and the aspirin-only group (n = 1649), and were stratified by risk subgroup and univariate risk factors. Stroke models from the Framingham Study and the Stroke Prognostic Instrument II were applied to subjects in the European Stroke Prevention Study 2 to categorize patients into risk groups. Results Compared with aspirin alone, aspirin plus extended-release Dipyridamole demonstrated a more pronounced efficacy in reducing the risk for stroke and vascular events among patients younger than 70 years; those with hypertension, prior stroke, or transient ischemic attack; current smokers; and those with any prior cardiovascular disease. Relative hazard reductions favored the combination of aspirin plus extended-release Dipyridamole, and were greatest for the high-risk Framingham Study group and the moderate-risk Stroke Prognostic Instrument II subgroup. Conclusion Aspirin plus extended-release Dipyridamole is more effective than aspirin alone at preventing stroke, and the difference in efficacy increases in higher-risk patients.

  • Dipyridamole for preventing recurrent ischemic stroke and other vascular events a meta analysis of individual patient data from randomized controlled trials
    Stroke, 2005
    Co-Authors: Jo Leonardibee, Philip M W Bath, M G Bousser, Antoni Davalos, Hanschristoph Diener, Bernard Guiraudchaumeil, Juhani Sivenius, Frank M Yatsu, Michael E Dewey
    Abstract:

    Background and Purpose— Results from randomized controlled trials of Dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Methods— Randomized controlled trials involving Dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of Dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Results— Recurrent stroke was reduced by Dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and Dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), Dipyridamole alone ...

  • european stroke prevention study 2 Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
    Journal of the Neurological Sciences, 1996
    Co-Authors: Hanschristoph Diener, Juhani Sivenius, Luis Cunha, C Forbes, P Smets, A Lowenthal
    Abstract:

    In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release Dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified-release Dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for Dipyridamole in reducing the risk of stroke (p < or = 0.001) and stroke or death combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone (p = 0.013); 16% with Dipyridamole alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone (p = 0.016); 15% with Dipyridamole alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA (p < 0.001) and Dipyridamole (p < 0.01) for preventing TIA. The risk reduction for the combination was 36% (p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in Dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or Dipyridamole. We conclude that (1) ASA 25 mg twice daily and Dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly; (3) low-dose ASA does not eliminate the propensity for induced bleeding.

Lance K Gould - One of the best experts on this subject based on the ideXlab platform.

  • regadenoson versus Dipyridamole hyperemia for cardiac pet imaging
    Jacc-cardiovascular Imaging, 2015
    Co-Authors: Nils P Johnson, Lance K Gould
    Abstract:

    Abstract Objectives The goal of this study was to compare regadenoson and Dipyridamole hyperemia for quantitative myocardial perfusion imaging. Background Regadenoson is commonly used for stress perfusion imaging. However, no study in nuclear cardiology has employed a paired design to compare quantitative hyperemic flow from regadenoson to more traditional agents such as Dipyridamole. Additionally, the timing of regadenoson bolus relative to tracer administration can be expected to affect quantitative flow. Methods Subjects underwent 2 rest/stress cardiac positron emission tomography scans using an Rb-82 generator. Each scan employed Dipyridamole and a second drug in random sequence, either regadenoson according to 5 timing sequences or repeated Dipyridamole. A validated retention model quantified absolute flow and coronary flow reserve. Results A total of 176 pairs compared regadenoson (126 pairs, split unevenly among 5 timing sequences) or repeated Dipyridamole (50 pairs). The cohort largely had few symptoms, only risk factors, and nearly normal relative uptake images, with 8% typical angina or dyspnea, 20% manifest coronary artery disease, and a minimum quadrant average of 80% (interquartile range: 76% to 83%) on Dipyridamole scans. Hyperemic flow varied among regadenoson timing sequences but showed consistently lower stress flow and coronary flow reserve compared with Dipyridamole. A timing sequence most similar to the regadenoson package insert achieved about 80% of Dipyridamole hyperemia, whereas further delaying radiotracer injection reached approximately 90% of Dipyridamole hyperemia. Because of the small numbers of pairs for each regadenoson timing protocol and a paucity of moderate or large perfusion defects, we did not observe a difference in relative uptake. Conclusions With the standard timing protocol from the package insert, regadenoson achieved only 80% of Dipyridamole hyperemia quantitatively imaged by cardiac positron emission tomography using Rb-82. A nonstandard protocol using a more delayed radionuclide injection after the regadenoson bolus improved its effect to 90% of Dipyridamole hyperemia.

  • physiological basis for angina and st segment change pet verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve
    Jacc-cardiovascular Imaging, 2011
    Co-Authors: Nils P Johnson, Lance K Gould
    Abstract:

    Objectives This study aimed to determine the quantitative low-flow threshold for stress-induced perfusion defects with severe angina and/or significant ST-segment depression during Dipyridamole hyperemia. Background Vasodilator stress reveals differences in regional perfusion without ischemia in most patients. However, in patients with a perfusion defect, angina, and/or significant ST-segment depression during Dipyridamole stress, quantitative absolute myocardial perfusion and coronary flow reserve (CFR) at the exact moment of definite ischemia have not been established. Defining these low-flow thresholds of angina or ST-segment changes may offer insight into physiological disease severity in patients with atherosclerosis. Methods Patients underwent rest–Dipyridamole stress positron emission tomography (PET) with absolute flow quantification in ml/min/g. Definite ischemia was defined as a new or worse perfusion defect during Dipyridamole stress with significant ST-segment depression and/or severe angina requiring pharmacological treatment. Indeterminate clinical features required only 1 of these 3 abnormalities. The comparison group included patients without prior myocardial infarction, or angina or electrocardiographic changes after Dipyridamole. Results In 1,674 sequential PET studies, we identified 194 (12%) with definite ischemia, 840 (50%) studies with no ischemia, and 301 (18%) that were clinically indeterminate. A vasodilator stress perfusion cutoff of 0.91 ml/min/g optimally separated definite from no ischemia with an area under the receiver-operator characteristic curve (AUC) of 0.98 and a CFR cutoff of 1.74 with an AUC = 0.91, reflecting excellent discrimination at the exact moment of definite ischemia. Conclusions Thresholds of low myocardial vasodilator stress perfusion in ml/min/g and CFR sharply separate patients with angina or ST-segment change from those without these manifestations of ischemia during Dipyridamole stress with excellent discrimination. Stress flow below 0.91 ml/min/g in Dipyridamole-induced PET perfusion defects causes significant ST-segment depression and/or severe angina. However, when the worst vasodilator stress flow exceeds 1.12 ml/min/g, these manifestations of ischemia occur rarely.

Heinrich R Schelbert - One of the best experts on this subject based on the ideXlab platform.

  • effect of caffeine on myocardial blood flow at rest and during pharmacological vasodilation
    The Journal of Nuclear Medicine, 1995
    Co-Authors: Morten Bottcher, Johannes Czernin, Karl T Sun, Michael E Phelps, Heinrich R Schelbert
    Abstract:

    Stress testing with intravenous injection of Dipyridamole is frequently used for noninvasive detection of coronary artery disease (CAD) with PET or SPECT. Dietary intake of caffeinated food, beverages or medication might alter both resting and Dipyridamole-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of Dipyridamole stress testing. Methods: To quantify the effect on myocardial blood flow at rest and during intravenous injection of Dipyridamole, 12 healthy volunteers (mean age 27 ± 6 yr) with low risk for CAD were studied with dynamic PET and a tracer kinetic model for 13N-ammonia after 24 hr of caffeine abstinence and after caffeine intake. Results: Caffeine tended to increase the rate pressure product from 6873 ± 1494 to 7566 ± 1102 (p = 0.051), whereas resting myocardial blood flow remained unchanged (0.61 ± 0.13 versus 0.58 ± 0.07 ml/g/min, p = ns). The heart rate response to Dipyridamole was inversely related to serum caffeine levels. Hyperemic blood flow (2.01 ± 0.46 versus 1.31 ± 0.0.38 ml/g/min; p

  • comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous Dipyridamole in normal men
    Journal of the American College of Cardiology, 1992
    Co-Authors: Sammy Chan, Johannes Czernin, Michael E Phelps, Richard C Brunken, Gerold Porenta, William Kuhle, Janine Krivokapich, Heinrich R Schelbert
    Abstract:

    Objective. This study compared quantitatively the efficacy of intravenous adenosine and Dipyridamole for pharmacologic induction of myocardial hyperemia. Background. Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous Dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared. Methods. Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model. Results. Myocardial blood flow at rest averaged 1.1 ± 0.2 ml/min per g and increased significantly to 4.4 ± 0.9 ml/min per g during adenosine and 43 ± 1.3 ml/min per g after Dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 ± 1.6 for adenosine and 4.0 ± 1.3 for Dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for Dipyridamole). in addition, the hyperemic responses to Dipyridamole and to adenosine differed by > 1 ml/min per g in nine subjects. Conclusions. Despite these inter- and istraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.

Carol E Cass - One of the best experts on this subject based on the ideXlab platform.

  • residue 33 of human equilibrative nucleoside transporter 2 is a functionally important component of both the Dipyridamole and nucleoside binding sites
    Molecular Pharmacology, 2005
    Co-Authors: Frank Visser, Jing Zhang, Taylor R Raborn, Stephen A Baldwin, James D Young, Carol E Cass
    Abstract:

    Human equilibrative nucleoside transporters 1 and 2 (hENT1 and hENT2) differ functionally in that hENT2 generally displays lower affinity for its nucleoside permeants and is less sensitive to inhibition by the coronary vasodilators dilazep and Dipyridamole. In previous work, we demonstrated that mutation of residues 33 (Met versus Ile) of hENT1 and hENT2 altered sensitivity to dilazep and Dipyridamole and that the hENT2 mutant (I33M) displayed a Km value for uridine that was lower than that of hENT2 and similar to that of hENT1 (J Biol Chem277:395-401, 2002). In this study, we report results of an in-depth investigation of the role of residue 33 in hENT2. We found that hENT2-I33M displayed decreased Km values for both pyrimidine and purine nucleosides and increased Vmax values for purine nucleosides. Cys or Ser at position 33 had similar effects on the kinetic parameters of hENT2 as Met, indicating that hydrophobic (Met and Cys) or hydrogen-bonding energy (Ser) contributed to permeant binding by these residues. hENT2-I33M and I33C displayed increased sensitivities to Dipyridamole compared with wild-type hENT2, hENT2-I33A, and hENT2-I33S, suggesting interaction of the sulfur atom of Met and Cys with aromatic moieties on Dipyridamole. hENT2-I33C was inhibited by the membrane-impermeant sulfhydryl reactive reagent p-chloromercuribenzyl sulfonate, and uridine, adenosine, and Dipyridamole protected against inhibition. Our results indicated that residue 33 resides in an extracellular domain as predicted by the current hENT2 topology model and suggested that it is a functionally important component of both the permeant and Dipyridamole binding sites.

  • mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sensitivity to inhibition of transport by dilazep and Dipyridamole
    Journal of Biological Chemistry, 2002
    Co-Authors: Frank Visser, Stephen A Baldwin, James D Young, Mark F Vickers, Amy M L Ng, Carol E Cass
    Abstract:

    Abstract Human equilibrative nucleoside transporters (hENT) 1 and 2 differ in that hENT1 is inhibited by nanomolar concentrations of Dipyridamole and dilazep, whereas hENT2 is 2 and 3 orders of magnitude less sensitive, respectively. When a yeast expression plasmid containing the hENT1 cDNA was randomly mutated and screened by phenotypic complementation in Saccharomyces cerevisiae to identify mutants with reduced sensitivity to dilazep, clones with a point mutation that converted Met33to Ile (hENT1-M33I) were obtained. Characterization of the mutant protein in S. cerevisiae and Xenopus laevisoocytes revealed that the mutant had less than one-tenth the sensitivity to dilazep and Dipyridamole than wild type hENT1, with no change in nitrobenzylmercaptopurine ribonucleoside (NBMPR) sensitivity or apparent uridine affinity. To determine whether the reciprocal mutation in hENT2 (Ile33 to Met) also altered sensitivity to dilazep and Dipyridamole, hENT2-I33M was created by site-directed mutagenesis. Although the resulting mutant (hENT2-I33M) displayed >10-fold higher dilazep and Dipyridamole sensitivity and >8-fold higher uridine affinity compared with wild type hENT2, it retained insensitivity to NBMPR. These data established that mutation of residue 33 (Met versus Ile) of hENT1 and hENT2 altered the dilazep and Dipyridamole sensitivities in both proteins, suggesting that a common region of inhibitor interaction has been identified.