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Conference Paper: Effect of thiazolidinediones on adenosine transport in vascular smooth muscle cells

TitleEffect of thiazolidinediones on adenosine transport in vascular smooth muscle cells
Authors
Issue Date2005
Citation
The 9th International Symposium on Mechanisms of Vasodilatation and Endothelium-Derived Hyperpolarizing Factors (EDHF 2005), Antwerp, Belgium, May-June 2005. In Journal of Vascular Research, 2005, v. 42 suppl. 1, p. 73, abstract no. PS1P17 How to Cite?
AbstractObjective: Thiazolidinediones are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferators-activated receptor γ (PPARγ) and stimulate the expression of insulinresponsive genes involved in glucose and lipid metabolism. These drugs also have vasodilatory and antiproliferative effects on vascular smooth muscle cells (VSMCs). However the mechanisms for these actions are not understood. Adenosine is a vasodilator. Equilibrative nucleoside transporter (ENT)-1, which is an Na+- independent and nitrobenzylmercaptopurine riboside (NBMPR)-sensitive nucleoside transporter, plays an important role in adenosine functions because it fine-tunes the local concentrations of adenosine in the vicinity of adenosine receptors. In the present study, the effects of three thiazolidinediones, troglitazone, pioglitazone and ciglitazone, on ENT1 in VSMCs were studied. Methods: The ENT1 activity in VSCMs was determined by the initial rate of [3H]adenosine uptake and [3H]NBMPR binding assay. The mRNA and protein expressions of ENT1 were detected by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Results: Incubating VSMCs for 48 hr with thiazolidinediones had no effect on ENT1 mRNA and protein levels. However, troglitazone inhibited [3H]adenosine uptake and [3H]NBMPR binding of VSMCs with IC50 values of 2.35 ± 0.35 µM and 3.99 ± 0.57 µM, respectively. This effect of troglitazone on ENT1 was PPARγ- independent and kinetic studies revealed that troglitazone was a competitive inhibitor of ENT1. In contrast, pioglitazone and ciglitazone had minimal effects on [3H]adenosine uptake by VSMCs. Troglitazone differs from pioglitazone and ciglitazone as its side-chain contains a vitamin E moiety. This difference in structure of troglitazone did not account for its inhibitory effect on ENT1 because vitamin E did not inhibit [3H]adenosine uptake by VSMCs. Conclusions: Troglitazone inhibits ENT1. It is suggested that troglitazone may alter the vascular effect of adenosine.
Persistent Identifierhttp://hdl.handle.net/10722/106813

 

DC FieldValueLanguage
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorTse, CMen_HK
dc.contributor.authorMan, RYKen_HK
dc.date.accessioned2010-09-25T23:31:29Z-
dc.date.available2010-09-25T23:31:29Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 9th International Symposium on Mechanisms of Vasodilatation and Endothelium-Derived Hyperpolarizing Factors (EDHF 2005), Antwerp, Belgium, May-June 2005. In Journal of Vascular Research, 2005, v. 42 suppl. 1, p. 73, abstract no. PS1P17en_HK
dc.identifier.urihttp://hdl.handle.net/10722/106813-
dc.description.abstractObjective: Thiazolidinediones are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferators-activated receptor γ (PPARγ) and stimulate the expression of insulinresponsive genes involved in glucose and lipid metabolism. These drugs also have vasodilatory and antiproliferative effects on vascular smooth muscle cells (VSMCs). However the mechanisms for these actions are not understood. Adenosine is a vasodilator. Equilibrative nucleoside transporter (ENT)-1, which is an Na+- independent and nitrobenzylmercaptopurine riboside (NBMPR)-sensitive nucleoside transporter, plays an important role in adenosine functions because it fine-tunes the local concentrations of adenosine in the vicinity of adenosine receptors. In the present study, the effects of three thiazolidinediones, troglitazone, pioglitazone and ciglitazone, on ENT1 in VSMCs were studied. Methods: The ENT1 activity in VSCMs was determined by the initial rate of [3H]adenosine uptake and [3H]NBMPR binding assay. The mRNA and protein expressions of ENT1 were detected by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Results: Incubating VSMCs for 48 hr with thiazolidinediones had no effect on ENT1 mRNA and protein levels. However, troglitazone inhibited [3H]adenosine uptake and [3H]NBMPR binding of VSMCs with IC50 values of 2.35 ± 0.35 µM and 3.99 ± 0.57 µM, respectively. This effect of troglitazone on ENT1 was PPARγ- independent and kinetic studies revealed that troglitazone was a competitive inhibitor of ENT1. In contrast, pioglitazone and ciglitazone had minimal effects on [3H]adenosine uptake by VSMCs. Troglitazone differs from pioglitazone and ciglitazone as its side-chain contains a vitamin E moiety. This difference in structure of troglitazone did not account for its inhibitory effect on ENT1 because vitamin E did not inhibit [3H]adenosine uptake by VSMCs. Conclusions: Troglitazone inhibits ENT1. It is suggested that troglitazone may alter the vascular effect of adenosine.-
dc.languageengen_HK
dc.relation.ispartofJournal of Vascular Researchen_HK
dc.titleEffect of thiazolidinediones on adenosine transport in vascular smooth muscle cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLeung, GPH: leung_pak_heng@hotmail.comen_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1159/000086311-
dc.identifier.hkuros103367en_HK
dc.identifier.volume42-
dc.identifier.issuesuppl. 1-
dc.identifier.spage73, abstract no. PS1P17en_HK
dc.identifier.epage73, abstract no. PS1P17-

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