Estudo dos efeitos de compostos doadores de sulfeto de hidrogênio (H2S) sobre o prurido agudo induzido pela ativação dos receptores ativados por proteases do tipo 2 (PAR-2) em camundongos.

Sanchez, Silvia Abigail Coavoy

doi:10.11606/D.42.2016.tde-16082016-090906

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Master's Dissertation

DOI

https://doi.org/10.11606/D.42.2016.tde-16082016-090906

Document

Master's Dissertation

Author

Sanchez, Silvia Abigail Coavoy (Catálogo USP)

Full name

Silvia Abigail Coavoy Sanchez

Institute/School/College

Instituto de Ciências Biomédicas

Knowledge Area

Pharmacology

Date of Defense

2016-03-16

Published

São Paulo, 2016

Supervisor

Muscara, Marcelo Nicolas (Catálogo USP)

Committee

Muscara, Marcelo Nicolas (President)
Ferreira, Heloisa Helena Araujo
Lopes, Luciana Biagini

Title in Portuguese

Estudo dos efeitos de compostos doadores de sulfeto de hidrogênio (H₂S) sobre o prurido agudo induzido pela ativação dos receptores ativados por proteases do tipo 2 (PAR-2) em camundongos.

Keywords in Portuguese

Camundongo
Prurido
Receptor ativado por protease-2 (PAR-2)
SLIGRL-NH₂
Sulfeto de hidrogênio (H₂S)

Abstract in Portuguese

Neste trabalho investigamos o efeito de doadores de H₂S no prurido agudo mediado por PAR-2 em camundongos. A injeção i.d. do agonista PAR-2 SLIGRL-NH₂, induziu prurido que não foi afetado pelo pré-tratamento com o antagonista H₁ pirilamina. A coinjeção dos doadores de H₂S GYY4137 (lento) ou NaHS (espontâneo) com SLIGRL-NH₂ reduziu significativamente o prurido (P<0,05). A glibenclamida (bloqueador de canais K_ATP) e o SNP (doador de NO), mas não o ODQ (inibidor da sGC), evitaram estes efeitos. O antagonista TRPA₁ HC-030031 reduziu significativamente o prurido induzido pelo SLIGRL-NH₂ (P<0,05), mas o prurido induzido pelo agonista TPRA₁ AITC não foi afetado por NaHS. Ensaios de Western blot mostraram que ambos PAR-2 e TRPA₁ são expressos constitutivamente na pele de camundongos. Nossos dados mostram que o prurido secundário à ativação do PAR-2 pode ser reduzido por H₂S, atuando via a abertura dos canais K_ATP e ativação da via NO-GMPc. Ademais, o receptor TRPA₁ pode mediar o prurido induzido por SLIGRL-NH₂, mas o H₂S não interfere nesta via.

Title in English

Study of the effects of hydrogen sulfide (H₂S) donors on acute pruritus induced by the activation of protease-activated receptor type-2 (PAR-2) in mice.

Keywords in English

Hydrogen sulfide (H₂S)
Mice
Protease-activated receptor 2 (PAR-2)
Pruritus
SLIGRL-NH₂

Abstract in English

In this study we investigated the effect of H₂S donors in PAR-2-mediated acute pruritus in mice. The i.d. injection of the PAR-2 agonist SLIGRL-NH₂ induced itching that was unaffected by pre-treatment with the H₁ antagonist pyrilamine. Co-injection of the H₂S donors GYY4137 (slow) or NaHS (spontaneous) with SLIGRL-NH₂ significantly reduced pruritis (P <0.05). Glibenclamide (a K_ATP channel blocker) and SNP (a NO donor), but not ODQ (a sGC inhibitor) prevented these effects. The TRPA₁ antagonist HC-030031 significantly reduced SLIGRL-NH₂-induced pruritus (P<0.05), but the pruritus induced by the TPRA₁ agonist AITC was unaffected by NaHS. Western blot assays showed that both TRPA₁ and PAR-2 are constitutively expressed in the mouse skin. Our data show that itching secondary to PAR-2 activation can be reduced by H₂S which acts via the opening of K_ATP channels and activation of the NO-cGMP pathway. Furthermore, TRPA₁ receptors may mediate SLIGRL-NH₂-induced pruritus, however, H₂S does not interfere with this pathway.

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Publishing Date

2016-08-16

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