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Article: The effect of adrenomedullin on the L-type calcium current in myocytes from septic shock rats: Signaling pathway

TitleThe effect of adrenomedullin on the L-type calcium current in myocytes from septic shock rats: Signaling pathway
Authors
KeywordsPertussis toxin
Protein kinase A inhibitor
Issue Date2007
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 2007, v. 293 n. 5, p. H2888-H2893 How to Cite?
AbstractAdrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions, particularly in septic shock. The intracellular mechanisms involved in the effect of ADM on adult rat ventricular myocytes are still to be elucidated. Ventricular myocytes were isolated from adult rats 4 h after an intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Membrane potential and L-type calcium current (ICa,L) were determined using whole cell patch-clamp methods. APD in LPS group was significantly shorter than control values (time to 50% repolarization: LPS, 169 ± 2 ms; control, 257 ± 2 ms, P < 0.05; time to 90% repolarization: LPS, 220 ± 2 ms; control, 305 ± 2 ms, P < 0.05). ICa,L density was significantly reduced in myocytes from the LPS group (-3.2 ± 0.8 pA/pF) compared with that of control myocytes (-6.7 ± 0.3 pA/pF, P < 0.05). The ADM antagonist ADM-(22-52) reversed the shortened APD and abolished the reduction of ICa,L in shock myocytes. In myocytes from control rats, incubating with ADM for 1 h induced a marked decrease in peak ICa,L density. This effect was reversed by ADM-(22-52). The G i protein inhibitor, pertussis toxin (PTX), the protein kinase A (PKA) inhibitor, KT-5720, and the specific cyclooxygenase 2 (COX-2) inhibitor, nimesulide, reversed the LPS-induced reduction in peak ICa,L. The results suggest a COX-2-involved PKA-dependent switch from Gs coupled to PTX-sensitive Gi coupling by ADM in adult rat ventricular myocytes. The present study delineates the intracellular pathways involved in ADM-mediated effects on ICa,L in adult rat ventricular myocytes and also suggests a role of ADM in sepsis. Copyright © 2007 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/78751
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, XHen_HK
dc.contributor.authorLi, GRen_HK
dc.contributor.authorBourreau, JPen_HK
dc.date.accessioned2010-09-06T07:46:20Z-
dc.date.available2010-09-06T07:46:20Z-
dc.date.issued2007en_HK
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 2007, v. 293 n. 5, p. H2888-H2893en_HK
dc.identifier.issn0363-6135en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78751-
dc.description.abstractAdrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions, particularly in septic shock. The intracellular mechanisms involved in the effect of ADM on adult rat ventricular myocytes are still to be elucidated. Ventricular myocytes were isolated from adult rats 4 h after an intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Membrane potential and L-type calcium current (ICa,L) were determined using whole cell patch-clamp methods. APD in LPS group was significantly shorter than control values (time to 50% repolarization: LPS, 169 ± 2 ms; control, 257 ± 2 ms, P < 0.05; time to 90% repolarization: LPS, 220 ± 2 ms; control, 305 ± 2 ms, P < 0.05). ICa,L density was significantly reduced in myocytes from the LPS group (-3.2 ± 0.8 pA/pF) compared with that of control myocytes (-6.7 ± 0.3 pA/pF, P < 0.05). The ADM antagonist ADM-(22-52) reversed the shortened APD and abolished the reduction of ICa,L in shock myocytes. In myocytes from control rats, incubating with ADM for 1 h induced a marked decrease in peak ICa,L density. This effect was reversed by ADM-(22-52). The G i protein inhibitor, pertussis toxin (PTX), the protein kinase A (PKA) inhibitor, KT-5720, and the specific cyclooxygenase 2 (COX-2) inhibitor, nimesulide, reversed the LPS-induced reduction in peak ICa,L. The results suggest a COX-2-involved PKA-dependent switch from Gs coupled to PTX-sensitive Gi coupling by ADM in adult rat ventricular myocytes. The present study delineates the intracellular pathways involved in ADM-mediated effects on ICa,L in adult rat ventricular myocytes and also suggests a role of ADM in sepsis. Copyright © 2007 the American Physiological Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_HK
dc.subjectPertussis toxinen_HK
dc.subjectProtein kinase A inhibitoren_HK
dc.subject.meshAdrenomedullin - administration & dosage - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCalcium - metabolismen_HK
dc.subject.meshCalcium Channels, L-Type - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshIon Channel Gating - drug effectsen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMyocytes, Cardiac - drug effects - metabolismen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Sprague-Dawleyen_HK
dc.subject.meshShock, Septic - metabolismen_HK
dc.subject.meshSignal Transduction - drug effectsen_HK
dc.titleThe effect of adrenomedullin on the L-type calcium current in myocytes from septic shock rats: Signaling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0363-6135&volume=293&issue=5&spage=H2888&epage=93&date=2007&atitle=The+effect+of+adrenomedullin+on+the+L-type+calcium+current+in+myocytes+from+septic+shock+rats:+Signaling+pathway.++++en_HK
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_HK
dc.identifier.emailBourreau, JP: bourreau@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.identifier.authorityBourreau, JP=rp00389en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1152/ajpheart.00312.2007en_HK
dc.identifier.pmid17766482-
dc.identifier.scopuseid_2-s2.0-36148964038en_HK
dc.identifier.hkuros139378en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36148964038&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume293en_HK
dc.identifier.issue5en_HK
dc.identifier.spageH2888en_HK
dc.identifier.epageH2893en_HK
dc.identifier.eissn1522-1539-
dc.identifier.isiWOS:000251400100032-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, XH=7410270356en_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK
dc.identifier.scopusauthoridBourreau, JP=7003927886en_HK

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