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Article: Physiological and pharmacological roles of vascular nucleoside transporters

TitlePhysiological and pharmacological roles of vascular nucleoside transporters
Authors
Keywordsadenosine
diabetes
hypertension
nucleoside transporters
vascular cells
Issue Date2012
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/
Citation
Journal Of Cardiovascular Pharmacology, 2012, v. 59 n. 1, p. 10-15 How to Cite?
AbstractAdenosine modulates various vascular functions such as vasodilatation and anti-inflammation. The local concentration of adenosine in the vicinity of adenosine receptors is fine tuned by 2 classes of nucleoside transporters: equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). In vascular smooth muscle cells, 95% of adenosine transport is mediated by ENT-1 and the rest by ENT-2. In endothelial cells, 60%, 10%, and 30% of adenosine transport are mediated by ENT-1, ENT-2, and CNT-2, respectively. In vitro studies show that glucose per se increases the expression level of ENT-1 via mitogen-activating protein kinase-dependent pathways. Similar results have been demonstrated in diabetic animal models. Hypertension is associated with the increased expression of CNT-2. It has been speculated that the increase in the activities of ENT-1 and CNT-2 may reduce the availability of adenosine to adenosine receptors, thereby weakening the vascular functions of adenosine. This may explain why patients with diabetes and hypertension suffer greater morbidity from ischemia and atherosclerosis. No oral hypoglycemic agents can inhibit ENTs, but an exception is troglitazone (a thiazolidinedione that has been withdrawn from the market). ENTs are also sensitive to dihydropyridine-type calcium-channel blockers, particularly nimodipine, which can inhibit ENT-1 in the nanomolar range. Those calcium-channel blockers are noncompetitive inhibitors of ENTs, probably working through the reversible interactions with allosteric sites. The nonsteroidal anti-inflammatory drug sulindac sulfide is a competitive inhibitor of ENT-1. In addition to their original pharmacological actions, it is believed that the drugs mentioned above may regulate vascular functions through potentiation of the effects of adenosine. © 2012 Lippincott Williams & Wilkins, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/146892
ISSN
2015 Impact Factor: 2.462
2015 SCImago Journal Rankings: 0.962
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong SAR769607
Funding Information:

Supported by the Research Grant Council General Research Fund of Hong Kong SAR (project code: 769607).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, RWSen_HK
dc.contributor.authorYang, Cen_HK
dc.contributor.authorSit, ASMen_HK
dc.contributor.authorLin, SYTen_HK
dc.contributor.authorHo, EYWen_HK
dc.contributor.authorLeung, GPHen_HK
dc.date.accessioned2012-05-23T05:48:51Z-
dc.date.available2012-05-23T05:48:51Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Cardiovascular Pharmacology, 2012, v. 59 n. 1, p. 10-15en_HK
dc.identifier.issn0160-2446en_HK
dc.identifier.urihttp://hdl.handle.net/10722/146892-
dc.description.abstractAdenosine modulates various vascular functions such as vasodilatation and anti-inflammation. The local concentration of adenosine in the vicinity of adenosine receptors is fine tuned by 2 classes of nucleoside transporters: equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). In vascular smooth muscle cells, 95% of adenosine transport is mediated by ENT-1 and the rest by ENT-2. In endothelial cells, 60%, 10%, and 30% of adenosine transport are mediated by ENT-1, ENT-2, and CNT-2, respectively. In vitro studies show that glucose per se increases the expression level of ENT-1 via mitogen-activating protein kinase-dependent pathways. Similar results have been demonstrated in diabetic animal models. Hypertension is associated with the increased expression of CNT-2. It has been speculated that the increase in the activities of ENT-1 and CNT-2 may reduce the availability of adenosine to adenosine receptors, thereby weakening the vascular functions of adenosine. This may explain why patients with diabetes and hypertension suffer greater morbidity from ischemia and atherosclerosis. No oral hypoglycemic agents can inhibit ENTs, but an exception is troglitazone (a thiazolidinedione that has been withdrawn from the market). ENTs are also sensitive to dihydropyridine-type calcium-channel blockers, particularly nimodipine, which can inhibit ENT-1 in the nanomolar range. Those calcium-channel blockers are noncompetitive inhibitors of ENTs, probably working through the reversible interactions with allosteric sites. The nonsteroidal anti-inflammatory drug sulindac sulfide is a competitive inhibitor of ENT-1. In addition to their original pharmacological actions, it is believed that the drugs mentioned above may regulate vascular functions through potentiation of the effects of adenosine. © 2012 Lippincott Williams & Wilkins, Inc.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/en_HK
dc.relation.ispartofJournal of Cardiovascular Pharmacologyen_HK
dc.subjectadenosineen_HK
dc.subjectdiabetesen_HK
dc.subjecthypertensionen_HK
dc.subjectnucleoside transportersen_HK
dc.subjectvascular cellsen_HK
dc.subject.meshAdenosine - metabolism-
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidal - administration and dosage - pharmacology - therapeutic use-
dc.subject.meshEquilibrative Nucleoside Transport Proteins - genetics - metabolism - physiology-
dc.subject.meshMembrane Transport Proteins - genetics - metabolism - physiology-
dc.subject.meshVascular Diseases - drug therapy - metabolism-
dc.titlePhysiological and pharmacological roles of vascular nucleoside transportersen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, GPH: gphleung@hkucc.hku.hken_HK
dc.identifier.emailLi, RWS: h0594069@hkusua.hku.hk-
dc.identifier.emailYang, C: yangcui@hku.hk-
dc.identifier.emailLin, YT: lytlin@hku.hk-
dc.identifier.emailHo, YW: eywho@graduate.hku.hk-
dc.identifier.authorityLeung, GPH=rp00234en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/FJC.0b013e31820eb788en_HK
dc.identifier.pmid21266914-
dc.identifier.scopuseid_2-s2.0-84855348866en_HK
dc.identifier.hkuros199414en_US
dc.identifier.hkuros203460-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855348866&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue1en_HK
dc.identifier.spage10en_HK
dc.identifier.epage15en_HK
dc.identifier.isiWOS:000298669500002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, RWS=7404722884en_HK
dc.identifier.scopusauthoridYang, C=36845005200en_HK
dc.identifier.scopusauthoridSit, ASM=54882241900en_HK
dc.identifier.scopusauthoridLin, SYT=37099469300en_HK
dc.identifier.scopusauthoridHo, EYW=54397134000en_HK
dc.identifier.scopusauthoridLeung, GPH=35963668200en_HK

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