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Article: Inhibitory effect of nonsteroidal anti-inflammatory drugs on adenosine transport in vascular smooth muscle cells

TitleInhibitory effect of nonsteroidal anti-inflammatory drugs on adenosine transport in vascular smooth muscle cells
Authors
KeywordsAdenosine transport
Smooth muscle cell
Sulindac
Issue Date2009
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejphar
Citation
European Journal Of Pharmacology, 2009, v. 612 n. 1-3, p. 15-20 How to Cite?
AbstractIt is generally accepted that the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) arises mainly from the inhibition of cyclooxygenase (COX). However, more evidence has suggested that certain pharmacological actions of NSAIDs may be mediated by COX-independent mechanisms. The present study investigated the effects of NSAIDs on adenosine uptake in human aortic smooth muscle cells (HASMCs). Among the NSAIDs tested (all at 100 μM), aspirin, ibuprofen and naproxen had no effect on [ 3H]adenosine uptake. Piroxicam inhibited [ 3H]adenosine uptake by 30%, while etodolac, indomethacin, ketoprofen, mefenamic acid and sulindac inhibited [ 3H]adenosine by 13-18%. Sulindac sulfide, an active metabolite of sulindac, inhibited [ 3H]adenosine uptake and [ 3H]nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding of HASMCs with IC 50 values of 40.67 ± 4.82 and 24.19 ± 3.76 μM, respectively. Kinetic studies revealed that sulindac sulfide was a competitive inhibitor of adenosine uptake. Using the nucleoside-transporter-deficient PK15NTD cells that stably express equilibrative nucleoside transport (ENT) 1 and ENT2, it was found that the inhibitory effect of sulindac sulfide on ENT1 was greater than that on ENT2. Sulindac sulfide increased the extracellular adenosine level. In addition, it inhibited the proliferation of HASMCs and this anti-proliferative effect could be abolished by adenosine A 2B receptor antagonist. Our results suggest that sulindac sulfide may exert pharmacological effects through the inhibition of adenosine uptake, which modulates the availability of adenosine in the vicinity of adenosine receptors. © 2009 Elsevier B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59548
ISSN
2015 Impact Factor: 2.73
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, RWSen_HK
dc.contributor.authorSeto, SWen_HK
dc.contributor.authorAu, ALSen_HK
dc.contributor.authorKwan, YWen_HK
dc.contributor.authorChan, SWen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorTse, CMen_HK
dc.contributor.authorLeung, GPHen_HK
dc.date.accessioned2010-05-31T03:52:30Z-
dc.date.available2010-05-31T03:52:30Z-
dc.date.issued2009en_HK
dc.identifier.citationEuropean Journal Of Pharmacology, 2009, v. 612 n. 1-3, p. 15-20en_HK
dc.identifier.issn0014-2999en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59548-
dc.description.abstractIt is generally accepted that the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) arises mainly from the inhibition of cyclooxygenase (COX). However, more evidence has suggested that certain pharmacological actions of NSAIDs may be mediated by COX-independent mechanisms. The present study investigated the effects of NSAIDs on adenosine uptake in human aortic smooth muscle cells (HASMCs). Among the NSAIDs tested (all at 100 μM), aspirin, ibuprofen and naproxen had no effect on [ 3H]adenosine uptake. Piroxicam inhibited [ 3H]adenosine uptake by 30%, while etodolac, indomethacin, ketoprofen, mefenamic acid and sulindac inhibited [ 3H]adenosine by 13-18%. Sulindac sulfide, an active metabolite of sulindac, inhibited [ 3H]adenosine uptake and [ 3H]nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding of HASMCs with IC 50 values of 40.67 ± 4.82 and 24.19 ± 3.76 μM, respectively. Kinetic studies revealed that sulindac sulfide was a competitive inhibitor of adenosine uptake. Using the nucleoside-transporter-deficient PK15NTD cells that stably express equilibrative nucleoside transport (ENT) 1 and ENT2, it was found that the inhibitory effect of sulindac sulfide on ENT1 was greater than that on ENT2. Sulindac sulfide increased the extracellular adenosine level. In addition, it inhibited the proliferation of HASMCs and this anti-proliferative effect could be abolished by adenosine A 2B receptor antagonist. Our results suggest that sulindac sulfide may exert pharmacological effects through the inhibition of adenosine uptake, which modulates the availability of adenosine in the vicinity of adenosine receptors. © 2009 Elsevier B.V. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/ejpharen_HK
dc.relation.ispartofEuropean Journal of Pharmacologyen_HK
dc.rightsEuropean Journal of Pharmacology. Copyright © Elsevier BV.en_HK
dc.subjectAdenosine transporten_HK
dc.subjectSmooth muscle cellen_HK
dc.subjectSulindacen_HK
dc.titleInhibitory effect of nonsteroidal anti-inflammatory drugs on adenosine transport in vascular smooth muscle cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0014-2999&volume=612&spage=15&epage=20&date=2009&atitle=Inhibitory+effect+of+nonsteroidal+anti-inflammatory+drugs+on+adenosine+transport+in+vascular+smooth+muscle+cellsen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ejphar.2009.04.017en_HK
dc.identifier.pmid19379728-
dc.identifier.scopuseid_2-s2.0-65549129242en_HK
dc.identifier.hkuros157519en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65549129242&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume612en_HK
dc.identifier.issue1-3en_HK
dc.identifier.spage15en_HK
dc.identifier.epage20en_HK
dc.identifier.isiWOS:000267150900003-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridLi, RWS=7404722884en_HK
dc.identifier.scopusauthoridSeto, SW=9941482400en_HK
dc.identifier.scopusauthoridAu, ALS=7005391144en_HK
dc.identifier.scopusauthoridKwan, YW=7005662153en_HK
dc.identifier.scopusauthoridChan, SW=7404255670en_HK
dc.identifier.scopusauthoridLee, SMY=35233892600en_HK
dc.identifier.scopusauthoridTse, CM=7103295076en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK

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