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Article: Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells

TitleEffect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells
Authors
KeywordsAdenosine
Diabetes
Nucleoside transporter
Smooth muscle cells
Thiazolidinediones
Troglitazone
Issue Date2005
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2005, v. 70 n. 3, p. 355-362 How to Cite?
AbstractThiazolidinediones are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor γ (PPARγ) and stimulating the expression of insulin-responsive genes involved in glucose and lipid metabolism. These drugs also have vasodilatory and anti-proliferative effects on vascular smooth muscle cells. However the mechanisms for these actions are not fully understood. Adenosine is a vasodilator and a substrate of equilibrative nucleoside transporters (ENT). The present study studied the effects of three thiazolidinediones, troglitazone, pioglitazone and ciglitazone, on ENT1 in the human aortic smooth muscle cells (HASMCs). Although incubating HASMCs for 48 h with thiazolidinediones had no effect on ENT1 mRNA and protein levels, troglitazone acutely inhibited [ 3H]adenosine uptake and [ 3H]NBMPR binding of HASMCs with IC 50 values of 2.35 ± 0.35 and 3.99 ± 0.57 μM, respectively. The 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 HASMCs. Troglitazone differs from pioglitazone and ciglitazone in that its side-chain contains a Vitamin E moiety. The difference in structure of troglitazone did not account for its inhibitory effect on ENT1 because Vitamin E did not inhibit [ 3H]adenosine uptake by HASMCs. Using the nucleoside transporter deficient PK15NTD cells stably expressing ENT1 and ENT2, it was found that troglitazone inhibited ENT1 but had no effect on ENT2. From these results, it is suggested that troglitazone may enhance the vasodilatory effect of adenosine by inhibiting ENT1. Pharmacologically, troglitazone is a novel inhibitor of ENT1. © 2005 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/80264
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, GPHen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorTse, CMen_HK
dc.date.accessioned2010-09-06T08:04:22Z-
dc.date.available2010-09-06T08:04:22Z-
dc.date.issued2005en_HK
dc.identifier.citationBiochemical Pharmacology, 2005, v. 70 n. 3, p. 355-362en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80264-
dc.description.abstractThiazolidinediones are a new class of anti-diabetic agents which increase insulin sensitivity by binding to the peroxisome proliferator-activated receptor γ (PPARγ) and stimulating the expression of insulin-responsive genes involved in glucose and lipid metabolism. These drugs also have vasodilatory and anti-proliferative effects on vascular smooth muscle cells. However the mechanisms for these actions are not fully understood. Adenosine is a vasodilator and a substrate of equilibrative nucleoside transporters (ENT). The present study studied the effects of three thiazolidinediones, troglitazone, pioglitazone and ciglitazone, on ENT1 in the human aortic smooth muscle cells (HASMCs). Although incubating HASMCs for 48 h with thiazolidinediones had no effect on ENT1 mRNA and protein levels, troglitazone acutely inhibited [ 3H]adenosine uptake and [ 3H]NBMPR binding of HASMCs with IC 50 values of 2.35 ± 0.35 and 3.99 ± 0.57 μM, respectively. The 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 HASMCs. Troglitazone differs from pioglitazone and ciglitazone in that its side-chain contains a Vitamin E moiety. The difference in structure of troglitazone did not account for its inhibitory effect on ENT1 because Vitamin E did not inhibit [ 3H]adenosine uptake by HASMCs. Using the nucleoside transporter deficient PK15NTD cells stably expressing ENT1 and ENT2, it was found that troglitazone inhibited ENT1 but had no effect on ENT2. From these results, it is suggested that troglitazone may enhance the vasodilatory effect of adenosine by inhibiting ENT1. Pharmacologically, troglitazone is a novel inhibitor of ENT1. © 2005 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.rightsBiochemical Pharmacology. Copyright © Elsevier Inc.en_HK
dc.subjectAdenosineen_HK
dc.subjectDiabetesen_HK
dc.subjectNucleoside transporteren_HK
dc.subjectSmooth muscle cellsen_HK
dc.subjectThiazolidinedionesen_HK
dc.subjectTroglitazoneen_HK
dc.titleEffect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=70&spage=355&epage=362&date=2005&atitle=Effect+of+thiazolidinediones+on+equilibrative+nucleoside+transporter-1+in+human+aortic+smooth+muscle+cells.en_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_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_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2005.05.010en_HK
dc.identifier.pmid15963471-
dc.identifier.scopuseid_2-s2.0-21344473476en_HK
dc.identifier.hkuros100441en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-21344473476&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue3en_HK
dc.identifier.spage355en_HK
dc.identifier.epage362en_HK
dc.identifier.isiWOS:000230605000004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.scopusauthoridTse, CM=7103295076en_HK

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