Molecular and pharmacological evidence for modulation of kinin B-1 receptor expression by endogenous glucocorticoids hormones in rats

Molecular and pharmacological evidence for modulation of kinin B-1 receptor expression by endogenous glucocorticoids hormones in rats

Autor Cabrini, Daniela A. Google Scholar
Campos, Maria M. Google Scholar
Tratsk, Karla S. Google Scholar
Merino, Vanessa F. Google Scholar
Silva Junior, José Antonio Autor UNIFESP Google Scholar
Souza, Glória EP Google Scholar
Avellar, Maria Christina Werneck Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Calixto, João B. Google Scholar
Instituição Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Resumo 1 the effect of endogenous glucocorticoid hormones on the expression of rat BI receptors was examined by means of molecular and pharmacological functional approaches.2 Rats were adrenalectomized (ADX), and 7 days after this procedure the intradermal injection of B-1 receptor agonist des-Arg(9)-BK produced a significant increase in the paw volume, while only a weak effect was observed in sham-operated animals. A similar increase in the contractile responses mediated by B-1 agonist des-Arg(9)-BK was also observed in the rat portal vein in vitro.3 Chemical ADX performed with mitotane (a drug that reduces corticosteroid synthesis) produced essentially the same up-regulation of B-1 receptors as that observed in ADX rats.4 the modulation of B-1 receptor expression was evaluated by ribonuclease protection assay. employing mRNA obtained from the lungs and paw of ADX rats.5 Additionally. both paw oedema and contraction of portal vein mediated by B-1 agonist des-Arg(9)-BK in ADX mts, were markedly inhibited by treatment with dexamethasone, or COX-2 inhibitor meloxican. or with the NF-kappaB inhibitor PDTC. Interestingly, the same degree of inhibition was achieved when the animals were treated with a combination of submaximal doses of dexamethasone and PDTC.6 the involvement of NF-kappaB pathway was further confirmed by mobility shift assay using nuclear extracts from lung, paw and heart of ADX rats. It was also confirmed that the treatment of ADX rats with dexamethasone. PDTC or dexamethasone plus PDTC completely inhibit NF-kappaB activation caused by absence of endogenous glucucorticoid.7 Together. the results or the present study provide, for the first rime, molecular and pharmacological evidence showing that B-1 kinin receptor expression can be regulated through endogenous glucocorticoids by a mechanism dependent on NF-kappaB pathway. Clinical significance of the present findings stem from evidence showing the importance of B-1 kinin receptors in the mediation of inflammatory and pain related responses.
Palavra-chave adrenal hormones
nuclear factor-kappa B
B-1-kinin receptor up-regulation
rat paw oedema
rat portal vein
ribonuclease protection assay
gel shift assay
des-Arg(9)-bradykinin
Idioma Inglês
Data de publicação 2001-01-01
Publicado em British Journal of Pharmacology. Basingstoke: Nature Publishing Group, v. 132, n. 2, p. 567-577, 2001.
ISSN 0007-1188 (Sherpa/Romeo, fator de impacto)
Publicador Nature Publishing Group
Extensão 567-577
Fonte http://dx.doi.org/10.1038/sj.bjp.0703846
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000166736500023
Endereço permanente http://repositorio.unifesp.br/handle/11600/26434

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