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Article: The modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl lidociane

TitleThe modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl lidociane
Authors
Issue Date1995
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 1995, v. 309 n. 3, p. 871-876 How to Cite?
AbstractMethyl lidocaine is an experimental anti-arrhythmic drug which has been shown to enhance the biosynthesis of phosphatidylinositol (PI) in the hamster heart, In this study, the effect of methyl lidocaine on enzymes involved in the biosynthesis of PI in the heart was examined. When the hamster heart was perfused with labelled methyl lidocaine, the majority of the compound was not metabolized after perfusion. The direct action of methyl lidocaine on an enzyme was studied by the presence of the drug in enzyme assays, whereas its indirect action was studied by assaying the enzyme activity in the heart after methyl lidocaine perfusion. CTP:phosphatidic acid cytidylyl-transferase, a rate-limiting enzyme in PI biosynthesis, was stimulated by methyl lidocaine in a direct manner. Kinetic studies revealed that methyl lidocaine caused a change in the affinity between the enzyme and phosphatidic acid and resulted in the enhancement of the reaction. Alternatively, acyl-CoA: lysophosphatidic acid acyltransferase, another key enzyme for PI biosynthesis, was not activated by the presence of methyl lidocaine. However, the enzyme activity was stimulated in hearts perfused with methyl lidocaine. The enhancement of the acyltransferase by methyl lidocaine perfusion was found to be mediated via the adenylate cyclase cascade with the elevation of the cyclic AMP level. The stimulation of protein kinase A activity by cyclic AMP resulted in the phosphorylation and activation of the acyltransferase, Interestingly, the activity of protein kinase C was not stimulated by methyl lidocaine perfusion. We conclude that the enhancement of PI biosynthesis by methyl lidocaine in the hamster heart resulted from the direct activation of the cytidylyltransferase, as well as the phosphorylation and subsequent activation of the acyltransferase.
Persistent Identifierhttp://hdl.handle.net/10722/171170
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLee, Een_US
dc.contributor.authorTardi, PGen_US
dc.contributor.authorMan, RYKen_US
dc.contributor.authorChoy, PCen_US
dc.date.accessioned2012-10-30T06:12:30Z-
dc.date.available2012-10-30T06:12:30Z-
dc.date.issued1995en_US
dc.identifier.citationBiochemical Journal, 1995, v. 309 n. 3, p. 871-876en_US
dc.identifier.issn0264-6021en_US
dc.identifier.urihttp://hdl.handle.net/10722/171170-
dc.description.abstractMethyl lidocaine is an experimental anti-arrhythmic drug which has been shown to enhance the biosynthesis of phosphatidylinositol (PI) in the hamster heart, In this study, the effect of methyl lidocaine on enzymes involved in the biosynthesis of PI in the heart was examined. When the hamster heart was perfused with labelled methyl lidocaine, the majority of the compound was not metabolized after perfusion. The direct action of methyl lidocaine on an enzyme was studied by the presence of the drug in enzyme assays, whereas its indirect action was studied by assaying the enzyme activity in the heart after methyl lidocaine perfusion. CTP:phosphatidic acid cytidylyl-transferase, a rate-limiting enzyme in PI biosynthesis, was stimulated by methyl lidocaine in a direct manner. Kinetic studies revealed that methyl lidocaine caused a change in the affinity between the enzyme and phosphatidic acid and resulted in the enhancement of the reaction. Alternatively, acyl-CoA: lysophosphatidic acid acyltransferase, another key enzyme for PI biosynthesis, was not activated by the presence of methyl lidocaine. However, the enzyme activity was stimulated in hearts perfused with methyl lidocaine. The enhancement of the acyltransferase by methyl lidocaine perfusion was found to be mediated via the adenylate cyclase cascade with the elevation of the cyclic AMP level. The stimulation of protein kinase A activity by cyclic AMP resulted in the phosphorylation and activation of the acyltransferase, Interestingly, the activity of protein kinase C was not stimulated by methyl lidocaine perfusion. We conclude that the enhancement of PI biosynthesis by methyl lidocaine in the hamster heart resulted from the direct activation of the cytidylyltransferase, as well as the phosphorylation and subsequent activation of the acyltransferase.en_US
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_US
dc.relation.ispartofBiochemical Journalen_US
dc.subject.meshAcyltransferases - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnti-Arrhythmia Agents - Pharmacologyen_US
dc.subject.meshBucladesine - Pharmacologyen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshCyclic Amp - Metabolismen_US
dc.subject.meshCyclic Amp-Dependent Protein Kinases - Metabolismen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshHeart - Drug Effectsen_US
dc.subject.meshLidocaine - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshMesocricetusen_US
dc.subject.meshMyocardium - Enzymology - Metabolismen_US
dc.subject.meshPhosphatidylinositols - Biosynthesisen_US
dc.subject.meshProtein Kinase C - Metabolismen_US
dc.titleThe modulation of phosphatidylinositol biosynthesis in hamster hearts by methyl lidocianeen_US
dc.typeArticleen_US
dc.identifier.emailMan, RYK:rykman@hkucc.hku.hken_US
dc.identifier.authorityMan, RYK=rp00236en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7639704-
dc.identifier.scopuseid_2-s2.0-0029112181en_US
dc.identifier.hkuros20680-
dc.identifier.volume309en_US
dc.identifier.issue3en_US
dc.identifier.spage871en_US
dc.identifier.epage876en_US
dc.identifier.isiWOS:A1995RL53800025-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLee, E=7406968133en_US
dc.identifier.scopusauthoridTardi, PG=36805754700en_US
dc.identifier.scopusauthoridMan, RYK=7004986435en_US
dc.identifier.scopusauthoridChoy, PC=7006633002en_US

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