Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

Autor Pesquero, João Bosco Autor UNIFESP Google Scholar
Araújo, Ronaldo de Carvalho Autor UNIFESP Google Scholar
Heppenstall, P. A. Google Scholar
Stucky, C. L. Google Scholar
Silva Junior, Jose Antonio Autor UNIFESP Google Scholar
Walther, T. Google Scholar
Oliveira, Suzana Macedo de Autor UNIFESP Google Scholar
Pesquero, J. L. Google Scholar
Paiva, Antonio Cechelli de Mattos Autor UNIFESP Google Scholar
Calixto, J. B. Google Scholar
Lewin, G. R. Google Scholar
Bader, M. Google Scholar
Instituição Max Delbruck Ctr Mol Med
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de Santa Catarina (UFSC)
Resumo Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. Two kinin receptors have been described, B1 and B2. the B2 receptor is constitutively expressed, and its targeted disruption leads to salt-sensitive hypertension and altered nociception. the B1 receptor is a heptahelical receptor distinct from the B2 receptor in that it is highly inducible by inflammatory mediators such as bacterial lipopolysaccharide and interleukins. To clarify its physiological function, we have generated mice with a targeted deletion of the gene for the B1 receptor. B1 receptor-deficient animals are healthy, fertile, and normotensive. in these mice, bacterial lipopolysaccharide-induced hypotension is blunted, and there is a reduced accumulation of polymorphonuclear leukocytes in inflamed tissue. Moreover, under normal noninflamed conditions, they are analgesic in behavioral tests of chemical and thermal nociception. Using whole-cell patch-clamp recordings, we show that the B1 receptor was not necessary for regulating the noxious heat sensitivity of isolated nociceptors. However, by using an in vitro preparation, we could show that functional B1 receptors are present in the spinal cord, and their activation can facilitate a nociceptive reflex. Furthermore, in B1 receptor-deficient mice, we observed a reduction in the activity-dependent facilitation (wind-up) of a nociceptive spinal reflex. Thus. the kinin gl receptor plays an essential physiological role in the initiation of inflammatory responses and the modulation of spinal cord plasticity that underlies the central component of pain. the B1 receptor therefore represents a useful pharmacological target especially for the treatment of inflammatory disorders and pain.
Idioma Inglês
Data 2000-07-05
Publicado em Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 97, n. 14, p. 8140-8145, 2000.
ISSN 0027-8424 (Sherpa/Romeo, fator de impacto)
Editor Natl Acad Sciences
Extensão 8140-8145
Fonte http://dx.doi.org/10.1073/pnas.120035997
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000088048400086
URI http://repositorio.unifesp.br/handle/11600/26344

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