Cited 0 times in Scipus Cited Count

Pharmacological profile of KR-33028, a highly selective inhibitor of Na+/H+ exchanger.

DC Field Value Language
dc.contributor.authorJung, YS-
dc.contributor.authorKim, MY-
dc.contributor.authorKim, MJ-
dc.contributor.authorOh, KS-
dc.contributor.authorYi, KY-
dc.contributor.authorLee, S-
dc.contributor.authorYoo, SE-
dc.contributor.authorLee, BH-
dc.date.accessioned2011-03-22T05:25:43Z-
dc.date.available2011-03-22T05:25:43Z-
dc.date.issued2006-
dc.identifier.issn0014-2999-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/1864-
dc.description.abstractWe evaluated the cardioprotective effects of 4-cyano (benzo[b]thiophene-2-carbonyl)guanidine (KR-33028), a recently developed inhibitor of the Na+/H+ exchanger (NHE), on hypoxia-induced H9c2 cell death and on perfused rat hearts subjected to ischemia/reperfusion. KR-33028 inhibited in a concentration-dependent manner the recovery from acidosis induced by an NH4Cl prepulse in PS120 fibroblast cells expressing the human NHE-1 isoform (IC50: 2.59 microM). Treatment with KR-33028 (1-10 microM) significantly decreased hypoxia-induced necrotic cell death and apoptotic cell death in H9c2 cells. KR-33028 significantly inhibited hypoxia-induced increases in cytosolic and mitochondrial Ca2+ level and cytochrome c release, and recovered hypoxia-induced Delta psi(m) reduction. In the perfused rat hearts subjected to 30 min of ischemia and 30 min of reperfusion, KR-33028 (1-10 microM) improved cardiac contractility, decreased lactate dehydrogenase release, and increased content of tissue ATP, creatine phosphate and glycogen in a concentration-dependent manner. In addition, KR-33028 did not produce significant acute or subacute toxicity in the rats at doses tested. Our results suggest that a novel NHE-1 inhibitor KR-33028 possesses potent cardioprotective effects with minimal toxicity and that the effects may be mediated by inhibition of intracellular Ca2+ overload and mitochondrial cell death pathway.-
dc.language.isoen-
dc.subject.MESHAdenosine Triphosphate-
dc.subject.MESHAmmonium Chloride-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis-
dc.subject.MESHBehavior, Animal-
dc.subject.MESHBinding, Competitive-
dc.subject.MESHCalcium-
dc.subject.MESHCardiotonic Agents-
dc.subject.MESHCell Hypoxia-
dc.subject.MESHCell Line-
dc.subject.MESHCytosol-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHErythrocyte Count-
dc.subject.MESHFemale-
dc.subject.MESHGlycogen-
dc.subject.MESHGuanidines-
dc.subject.MESHHeart-
dc.subject.MESHHumans-
dc.subject.MESHHydrogen-Ion Concentration-
dc.subject.MESHIn Situ Nick-End Labeling-
dc.subject.MESHMale-
dc.subject.MESHMitochondria-
dc.subject.MESHMyocardial Reperfusion Injury-
dc.subject.MESHMyocardium-
dc.subject.MESHOrgan Size-
dc.subject.MESHPerfusion-
dc.subject.MESHPhosphocreatine-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHReceptors, Cell Surface-
dc.subject.MESHSodium-Hydrogen Antiporter-
dc.subject.MESHSpleen-
dc.subject.MESHThiophenes-
dc.titlePharmacological profile of KR-33028, a highly selective inhibitor of Na+/H+ exchanger.-
dc.typeArticle-
dc.identifier.pmid16516883-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00070-7-
dc.contributor.affiliatedAuthor정, 이숙-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.ejphar.2006.01.041-
dc.citation.titleEuropean journal of pharmacology-
dc.citation.volume535-
dc.citation.number1-3-
dc.citation.date2006-
dc.citation.startPage220-
dc.citation.endPage227-
dc.identifier.bibliographicCitationEuropean journal of pharmacology, 535(1-3). : 220-227, 2006-
dc.identifier.eissn1879-0712-
dc.relation.journalidJ000142999-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Files in This Item:
There are no files associated with this item.

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse