Neuronal differentiation of P19 embryonal carcinoma cells modulates kinin B2 receptor gene expression and function

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dc.contributor.authorMartins, Antonio Henrique Baccin [UNIFESP]
dc.contributor.authorResende, R. R.
dc.contributor.authorMajumder, P.
dc.contributor.authorFaria, M.
dc.contributor.authorCasarini, Dulce Elena [UNIFESP]
dc.contributor.authorTarnok, A.
dc.contributor.authorColli, W.
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorUlrich, Alexander Henning [UNIFESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Leipzig
dc.date.accessioned2016-01-24T12:37:52Z
dc.date.available2016-01-24T12:37:52Z
dc.date.issued2005-05-20
dc.description.abstractKinins are vasoactive oligopeptides generated upon proteolytic cleavage of low and high molecular weight kininogens by kallikreins. These peptides have a well established signaling role in inflammation and homeostasis. Nevertheless, emerging evidence suggests that bradykinin and other kinins are stored in the central nervous system and may act as neuromediators in the control of nociceptive response. Here we show that the kinin-B2 receptor (B2BKR) is differentially expressed during in vitro neuronal differentiation of P19 cells. Following induction by retinoic acid, cells form embryonic bodies and then undergo neuronal differentiation, which is complete after 8 and 9 days. Immunochemical staining revealed that B2BKR protein expression was below detection limits in nondifferentiated P19 cells but increased during the course of neuronal differentiation and peaked on days 8 and 9. Measurement of [Ca2+](i) in the absence and presence of bradykinin showed that most undifferentiated cells are unresponsive to bradykinin application, but following differentiation, P19 cells express high molecular weight neurofilaments, secrete bradykinin into the culture medium, and respond to bradykinin application with a transient increase in [Ca2+](i). However, inhibition of B2BKR activity with HOE-140 during early differentiation led to a decrease in the size of embryonic bodies formed. Pretreatment of differentiating P19 cells with HOE-140 on day 5 resulted in a reduction of the calcium response induced by the cholinergic agonist carbamoylcholine and decreased expression levels of M1-M3 muscarinic acetylcholine receptors, indicating crucial functions of the B2BKR during neuronal differentiation.en
dc.description.affiliationUniv São Paulo, Inst Quim, Dept Bioquim, BR-05513970 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Nefrol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Leipzig, Cardiac Ctr Leipzig, D-04280 Leipzig, Germany
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Nefrol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent19576-19586
dc.identifierhttp://dx.doi.org/10.1074/jbc.M502513200
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 280, n. 20, p. 19576-19586, 2005.
dc.identifier.doi10.1074/jbc.M502513200
dc.identifier.issn0021-9258
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/28305
dc.identifier.wosWOS:000229113700020
dc.language.isoeng
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleNeuronal differentiation of P19 embryonal carcinoma cells modulates kinin B2 receptor gene expression and functionen
dc.typeinfo:eu-repo/semantics/article
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