Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Lima Júnior, Francisco José Batista de
Orientador(a): Magalhães, Pedro Jorge Caldas
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/38649
Resumo: β-Phenylethylamine (β-PEA) was considered for a long time an indirect sympathomimetic compound. Cloning of trace amine-associated receptors (TAAR) unmasked β-PEA as neurotransmitter, but the role of TAAR in peripheral tissues is yet unsolved. Searching for a response related to a recruitment of TAAR induced by β-PEA, we compared its effects on rat muscle preparations with those typically elicited by the adrenergic agonists phenylephrine or isoproterenol. At lower concentrations, β-PEA relaxed aortic rings previously contracted with phenylephrine in a propranolol-independent manner. In aortic rings under resting tonus, β-PEA induced contraction, effect insensitive to prazosin and observed only at higher β-PEA concentrations. Like phenylephrine, β-PEA induced prazosin-sensitive contractions in spleen strips. In isolated atrium, β-PEA stimulated atrial chronotropism with a lesser potency than isoproterenol but in a propranolol-dependent manner. In tracheal rings, β-PEA induced relaxation not inhibited by propranolol. Under resting tonus, gastric fundus strips contracted in response to β-PEA, an effect that involved extracellular Ca2+ recruitment. Phenylephrine was inert and isoproterenol was relaxant on fundic strips, findings suggestive that β-PEA-elicited contractions did not involve adrenergic receptors. Antagonists of 5-HT receptors, but not EPPTB, a TAAR1 antagonist, inhibited β-PEA-induced contractions on fundic strips. When fundic strips were previously contracted by KCl, β-PEA exerted relaxant effects refractory to 5-HT antagonists, but inhibited by the adenylyl cyclase inhibitor MDL-12,330A.Thus, β-PEA contracted rat gastric fundus with involvement of 5-HT receptors. Under KCl-elicited stimulus, β-PEA-induced relaxation through activation of TAAR1 signalling via the adenylyl cyclase pathway , suggesting a dual role for β-PEA on gastric fundus smooth muscle.
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spelling Lima Júnior, Francisco José Batista deMagalhães, Pedro Jorge Caldas2019-01-03T11:11:00Z2019-01-03T11:11:00Z2019-01-02LIMA JUNIOR, F. J. B. Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos. 2018. 88 f. Tese (Doutorado em Farmacologia). Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/38649β-Phenylethylamine (β-PEA) was considered for a long time an indirect sympathomimetic compound. Cloning of trace amine-associated receptors (TAAR) unmasked β-PEA as neurotransmitter, but the role of TAAR in peripheral tissues is yet unsolved. Searching for a response related to a recruitment of TAAR induced by β-PEA, we compared its effects on rat muscle preparations with those typically elicited by the adrenergic agonists phenylephrine or isoproterenol. At lower concentrations, β-PEA relaxed aortic rings previously contracted with phenylephrine in a propranolol-independent manner. In aortic rings under resting tonus, β-PEA induced contraction, effect insensitive to prazosin and observed only at higher β-PEA concentrations. Like phenylephrine, β-PEA induced prazosin-sensitive contractions in spleen strips. In isolated atrium, β-PEA stimulated atrial chronotropism with a lesser potency than isoproterenol but in a propranolol-dependent manner. In tracheal rings, β-PEA induced relaxation not inhibited by propranolol. Under resting tonus, gastric fundus strips contracted in response to β-PEA, an effect that involved extracellular Ca2+ recruitment. Phenylephrine was inert and isoproterenol was relaxant on fundic strips, findings suggestive that β-PEA-elicited contractions did not involve adrenergic receptors. Antagonists of 5-HT receptors, but not EPPTB, a TAAR1 antagonist, inhibited β-PEA-induced contractions on fundic strips. When fundic strips were previously contracted by KCl, β-PEA exerted relaxant effects refractory to 5-HT antagonists, but inhibited by the adenylyl cyclase inhibitor MDL-12,330A.Thus, β-PEA contracted rat gastric fundus with involvement of 5-HT receptors. Under KCl-elicited stimulus, β-PEA-induced relaxation through activation of TAAR1 signalling via the adenylyl cyclase pathway , suggesting a dual role for β-PEA on gastric fundus smooth muscle.β-feniletilamina (β-FEA) foi considerada por muito tempo um composto simpaticomimético indireto. Com a descoberta de receptores associados a aminas-traço (TAAR) revelou-se uma função como ligante, mas o papel do TAAR em tecidos periféricos ainda não foi solucionado. Procurando por respostas relacionadas ao recrutamento de TAAR, foram comparadas respostas da β-FEA aos agonistas adrenérgicos fenilefrina e isoproterenol. Em baixas concentrações, β-FEA relaxou anéis de aorta previamente contraídos com fenilefrina sem interferência de propranolol. Sob tensão de repouso, β-FEA induziu contração, efeito insensível ao prazosin e observado em altas concentrações. De forma análoga a fenilefrina, β-FEA induziu contrações em hemissecções de baço sensíveis ao prazosin. β-FEA estimulou cronotropismo positivo em átrio direto isolado com potência inferior ao isoproterenol, mas sensível ao propranolol, enquanto em anéis de traqueia induziu relaxamento independente de propranolol. Em tensão basal, tiras de fundo de estômago contraíram em resposta a β-FEA, um efeito que envolve influxo de Ca2+ extracelular. Fenilefrina foi inerte e isoproterenol relaxou tiras de fundo, achados sugestivos as contrações induzidas por β-FEA não envolvia receptores adrenérgicos. Antagonistas serotoninérgicos, mas não o antagonista de TAAR1, inibiram as contrações induzidas por β-FEA em tiras de fundo gástrico. Quando essas tiras foram previamente contraídas com KCl, β-FEA passou a exercer efeitos relaxantes, refratários aos antagonistas serotoninérgicos, mas inibidos pelo inibidor de adenilato ciclase, MDL 12,330A. Portanto, contração de β-FEA em fundo gástrico parece envolver receptores de serotonina, e quando estimulada com elevadas concentrações de KCl, β-FEA induz relaxamento aparentemente pela ativação de TAAR1 e produção de AMPc, confirmando um papel dual para β-FEA na musculatura lisa de fundo gástrico.AortaAdrenérgicoÁtrios do CoraçãoInvestigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratosStudy of β-Phenylethylamine on different isolated organs contratility and mechanism for dual effect on isolated strips of rat stomach fundusinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/38649/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINAL2018_tese_fjblimajunior.pdf2018_tese_fjblimajunior.pdfapplication/pdf3392467http://repositorio.ufc.br/bitstream/riufc/38649/1/2018_tese_fjblimajunior.pdfad507c7f1bf512db9b00a8c40a806c9fMD51riufc/386492019-10-23 11:47:30.333oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-23T14:47:30Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
dc.title.en.pt_BR.fl_str_mv Study of β-Phenylethylamine on different isolated organs contratility and mechanism for dual effect on isolated strips of rat stomach fundus
title Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
spellingShingle Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
Lima Júnior, Francisco José Batista de
Aorta
Adrenérgico
Átrios do Coração
title_short Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
title_full Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
title_fullStr Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
title_full_unstemmed Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
title_sort Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos
author Lima Júnior, Francisco José Batista de
author_facet Lima Júnior, Francisco José Batista de
author_role author
dc.contributor.author.fl_str_mv Lima Júnior, Francisco José Batista de
dc.contributor.advisor1.fl_str_mv Magalhães, Pedro Jorge Caldas
contributor_str_mv Magalhães, Pedro Jorge Caldas
dc.subject.por.fl_str_mv Aorta
Adrenérgico
Átrios do Coração
topic Aorta
Adrenérgico
Átrios do Coração
description β-Phenylethylamine (β-PEA) was considered for a long time an indirect sympathomimetic compound. Cloning of trace amine-associated receptors (TAAR) unmasked β-PEA as neurotransmitter, but the role of TAAR in peripheral tissues is yet unsolved. Searching for a response related to a recruitment of TAAR induced by β-PEA, we compared its effects on rat muscle preparations with those typically elicited by the adrenergic agonists phenylephrine or isoproterenol. At lower concentrations, β-PEA relaxed aortic rings previously contracted with phenylephrine in a propranolol-independent manner. In aortic rings under resting tonus, β-PEA induced contraction, effect insensitive to prazosin and observed only at higher β-PEA concentrations. Like phenylephrine, β-PEA induced prazosin-sensitive contractions in spleen strips. In isolated atrium, β-PEA stimulated atrial chronotropism with a lesser potency than isoproterenol but in a propranolol-dependent manner. In tracheal rings, β-PEA induced relaxation not inhibited by propranolol. Under resting tonus, gastric fundus strips contracted in response to β-PEA, an effect that involved extracellular Ca2+ recruitment. Phenylephrine was inert and isoproterenol was relaxant on fundic strips, findings suggestive that β-PEA-elicited contractions did not involve adrenergic receptors. Antagonists of 5-HT receptors, but not EPPTB, a TAAR1 antagonist, inhibited β-PEA-induced contractions on fundic strips. When fundic strips were previously contracted by KCl, β-PEA exerted relaxant effects refractory to 5-HT antagonists, but inhibited by the adenylyl cyclase inhibitor MDL-12,330A.Thus, β-PEA contracted rat gastric fundus with involvement of 5-HT receptors. Under KCl-elicited stimulus, β-PEA-induced relaxation through activation of TAAR1 signalling via the adenylyl cyclase pathway , suggesting a dual role for β-PEA on gastric fundus smooth muscle.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-01-03T11:11:00Z
dc.date.available.fl_str_mv 2019-01-03T11:11:00Z
dc.date.issued.fl_str_mv 2019-01-02
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv LIMA JUNIOR, F. J. B. Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos. 2018. 88 f. Tese (Doutorado em Farmacologia). Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/38649
identifier_str_mv LIMA JUNIOR, F. J. B. Investigação da β-feniletilamina sobre contratilidade de diferentes órgãos isolados e mecanismo responsável por efeito dual em tiras isoladas de fundo de estômago de ratos. 2018. 88 f. Tese (Doutorado em Farmacologia). Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
url http://www.repositorio.ufc.br/handle/riufc/38649
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