Evidence For Two Atypical Conformations Of Beta-adrenoceptors And Their Interaction With Gi Proteins.

dc.creatorSantos, Iraídes N
dc.creatorSumitame, Marie
dc.creatorCaceres, Viviane M
dc.creatorMoreira, Marilia F
dc.creatorKrieger, Marta H
dc.creatorSpadari-Bratfisch, Regina C
dc.date2005-Apr
dc.date2015-11-27T13:02:05Z
dc.date2015-11-27T13:02:05Z
dc.date.accessioned2018-03-29T01:00:48Z
dc.date.available2018-03-29T01:00:48Z
dc.identifierEuropean Journal Of Pharmacology. v. 513, n. 1-2, p. 109-18, 2005-Apr.
dc.identifier0014-2999
dc.identifier10.1016/j.ejphar.2005.03.008
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/15878715
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/196250
dc.identifier15878715
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1296483
dc.descriptionIn this study, we investigated whether the responses of right atria from sinoaortic denervated rats to CGP12177 (4(3-t-butylamino-2-hydroxypropoxy benzidimidazole-2 one, hydrochloride)), isoprenaline and norepinephrine desensitized in parallel and whether CGP12177 interacted with distinct conformations of beta-adrenoceptors. Right atria from rats 48 h after sinoaortic denervation were subsensitive to isoprenaline, norepinephrine and CGP12177. One week after sinoaortic denervation, the sensitivity to CGP12177 had recovered whereas the responses to isoprenaline and norepinephrine were still subsensitive, suggesting that the binding sites for these molecules showed independent behavior. In atria from 48 h sinoaortic-denervated rats, propranolol or 3 microM CGP20712A (2-hydroxy-5(2-((2-hydroxy-3-(4-((methyl-4-trifluormethyl)1H imidazole-2-yl)-phenoxypropyl) amino) ethoxy)-benzamide monomethane sulphonate)) blocked the responses to 10 nM-1 microM CGP12177 and steepened the curves. The concentration-response curves to CGP12177 in the presence of ICI118,551 (erythro-DL-1(-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol) were biphasic, suggesting that CGP12177 interacted with at least two conformations of beta-adrenoceptors that showed negative cooperativism, one acting through beta(2)-adrenoceptor-Gi and the other via beta(1)-adrenoceptor-Gs. This hypothesis was confirmed in right atria from sinoaortic-denervated rats treated with pertussis toxin.
dc.description513
dc.description109-18
dc.languageeng
dc.relationEuropean Journal Of Pharmacology
dc.relationEur. J. Pharmacol.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAdrenergic Alpha-agonists
dc.subjectAdrenergic Beta-agonists
dc.subjectAdrenergic Beta-antagonists
dc.subjectAnimals
dc.subjectDose-response Relationship, Drug
dc.subjectGtp-binding Protein Alpha Subunits, Gi-go
dc.subjectHeart
dc.subjectHeart Atria
dc.subjectImidazoles
dc.subjectIn Vitro Techniques
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMyocardial Contraction
dc.subjectNorepinephrine
dc.subjectPertussis Toxin
dc.subjectPropanolamines
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectReceptors, Adrenergic, Beta
dc.subjectReceptors, Adrenergic, Beta-1
dc.titleEvidence For Two Atypical Conformations Of Beta-adrenoceptors And Their Interaction With Gi Proteins.
dc.typeArtículos de revistas


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