Central effects of the preservative, methylparaben. In vivo activation of cAMP-specific phosphodiesterase and reduction of cortical cAMP

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dc.contributor.authorHarvey B.H.
dc.contributor.authorCarstens M.E.
dc.contributor.authorTaljaard J.J.F.
dc.date.accessioned2011-05-15T16:01:18Z
dc.date.available2011-05-15T16:01:18Z
dc.date.issued1992
dc.description.abstractThe phenolic preservative, methylparaben (MPB), has in the past been demonstrated to harbour definite pharmacological effects. In an attempt to examine the possible central effects of MPB, notably on cyclic nucleotides and cyclic nucleotide phosphodiesterase (PDE; EC 3.1.4.17), rats were orally treated with the drug (0.4% in rat food) for 3 weeks with cortex extracts being used for the various determinations. Three isozymes were identified by DEAE-cellulose anion exchange chromatography, namely the calmodulin/calcium-stimulated form or PDE I (peak I), the cGMP-stimulated form or PDE II (peak II), and an independent form not affected by either calmodulin or cGMP also known as PDE IV (peak III). The presence of MPB induced a significant decrease in cortical cAMP, as well as strongly stimulating the activity of PDE IV (peak III). In addition, a small, yet significant, increase in cGMP levels was observed. Since no increase in cGMP hydrolysis was observed, we conclude that chronic ingestion of MPB induces a preference for cAMP hydrolysis, which was confirmed by the increase in PDE IV (peak III) activity. PDE IV is a membrane-bound, low K(m) PDE exhibiting high selectivity for cAMP hydrolysis. While there was an increase in cGMP, we failed to observe an increase in the activity of the cGMP-stimulated PDE (PDE II). These data are discussed with reference to the possible membrane effects of MPB allowing it to alter both the kinetic properties of PDE IV with the resultant effects on cAMP, as well as a means whereby it may activate guanyl cyclase and increase cGMP.
dc.description.versionArticle
dc.identifier.citationBiochemical Pharmacology
dc.identifier.citation44
dc.identifier.citation6
dc.identifier.issn62952
dc.identifier.other10.1016/0006-2952(92)90367-R
dc.identifier.urihttp://hdl.handle.net/10019.1/11907
dc.subjectcalmodulin
dc.subjectcyclic amp
dc.subjectcyclic amp phosphodiesterase
dc.subjectcyclic gmp
dc.subjectcyclic gmp phosphodiesterase
dc.subjectcyclic nucleotide
dc.subjectcyclic nucleotide phosphodiesterase
dc.subjectisoenzyme
dc.subjectmethyl paraben
dc.subjectpreservative
dc.subjectanimal tissue
dc.subjectanion exchange chromatography
dc.subjectarticle
dc.subjectbrain cortex
dc.subjectcontrolled study
dc.subjectenzyme activity
dc.subjecthydrolysis
dc.subjectmale
dc.subjectneurochemistry
dc.subjectnonhuman
dc.subjectoral drug administration
dc.subjectpriority journal
dc.subjectrat
dc.subject3',5'-Cyclic-Nucleotide Phosphodiesterase
dc.subjectAnimal
dc.subjectCerebral Cortex
dc.subjectCyclic AMP
dc.subjectCyclic GMP
dc.subjectDown-Regulation
dc.subjectEnzyme Activation
dc.subjectIsoenzymes
dc.subjectMale
dc.subjectParabens
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSupport, Non-U.S. Gov't
dc.titleCentral effects of the preservative, methylparaben. In vivo activation of cAMP-specific phosphodiesterase and reduction of cortical cAMP
dc.typeArticle
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