Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2011 / Made available in DSpace on 2012-10-26T05:38:18Z (GMT). No. of bitstreams: 1
290484.pdf: 2223179 bytes, checksum: 6cba3254b3fc511eda0220e4973d0485 (MD5) / O presente trabalho reproduziu o modelo experimental descrito por Shimada e Lamotte, (2008), e o utilizou para diferenciar e quantificar as respostas de coceira ou nocicepção à ET-1 na face de camundongos. A histamina causou acessos de coceira com efeito máximo em 50 mg, sem causar movimentos de limpeza. A capsaicina causou nocicepção (movimentos de limpeza facial) na dose máxima de 40 mg, porém, não promoveu acessos de coceira. A co-injeção i.d. de histamina (50 mg) juntamente com capsaicina (10 mg) resultou em diminuição ambas as repostas. A injeção i.d. de ET-1 (3 - 60 pmol) induziu tanto coceira, quanto nocicepção, proporcionais à dose administrada. A coceira induzida pela ET-1 (30 pmol) foi inibida pelo antagonista de receptores ETA BQ-123 (10 nmol, i.d., 5 min antes) e aumentada pelo antagonista de receptores ETB BQ-788 (10 nmol, i.d, 5 min antes). A injeção de BQ-123 não inibiu a nocicepção, porém, a coinjeção de ambos os antagonistas reduziu a hipernocicepçãoà ET-1 causada por BQ-788. A co-injeção com naltrexona (5 mg, i.d.) não alterou a coceira, mas aumentou a nocicepção. Porém os antagonistas seletivos µ (CTOP, 20 nmol) e . (Nor-BNI, 68 nmol) opióides aumentaram os acessos de coceira sem alterarem a nocicepção. Enquanto a coceira causada pela ET-1 foi inibida pelo agonista seletivo µ opióide (DAMGO, 100 nmol), mas não pelo agonista seletivo . opióide (U50488-H, 100 nmol) a nocicepção foi reduzida por ambas as dorgas. A loratadina (10 mg/Kg, i.p., 60 min antes), antagonista dos receptores H1 para histamina reduziu ambas as respostas à ET-1. A análise histológica revelou aumento no número de mastócitos intactos e degranulados na derme, 15 e 30 min após injeção de ET-1. Assim, ambas as respostas à ET-1, neste modelo, são mediadas por receptores ETA e por mastócitos, sendo dependentes de histamina. Este efeito parece ser limitado pela ativação de receptores ETB acoplados a
liberaç0ão local de opióides. / This study aimed to replicate the experimental model described by Shimada and Lamotte (2008) and use it to differentiate and quantify the itch and nociception responses promoted by ET-1 in the check of mice. Histamine elicited scratching bouts, with maximal effect at 50 mg, but did not induce wipes bouts. Capsaicin evoked wiping responses in the maximum dose of (40 mg), but did not causes scratching. Responses induced by i.d. co-injection of histamine (50 mg) with capsaicin (10 mg) were reduce in comparison to those promoted by each drug alone. The i.d injection of ET-1 (3 - 60 pmol) induced both sctraching and wiping response, with maximum response at a dose of 60 pmol. Scratching induced by ET-1 (30 pmol) as inhibited by ETA receptor antagonist, BQ- 123 (10 nmol, i.d, 5 min before) and incresead by ETB receptor antagonist, BQ-788 (10 nmol, i.d, 5 min before). The BQ-123 treatment did not inhibit the wiping, but the co-injection of both antagonists reduced hypernociception to ET-1 induced by BQ 788. Co-injected with ET-1, naltrexone (5 mg, i.d.), did not alter the scratching bouts, but increase wiping. However, the selective antagonist as ì opioids (CTOP, 20 nmol) and ê opioid receptor (Nor-BNI, 68 nmol) augmented the scratching bouts without affecting wiping. While the scratching bouts were inhibited only by the selective ì opioid agonist (DAMGO,100 nmol) but not ê selective agonist (U50488-H,100 nmol) the wiping was reduced by both opioid agonist. The treatment with loratadine (10 mg/kg, i.p., 60 min before) reduced both ET-1 induced responses. Cheek skin sections obtained 15 and 30 min after ET-1 i.d. injection showed an increased number of intact and degranulated mast cells. Thus, both responses to ET-1 in this model are mediated by ETA receptors, being mediated by mast cells and histamine-dependent. This effect can be limited by activation of anti-pruritic ETB receptors coupled to local opioid release.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsc.br:123456789/95754 |
| Date | 26 October 2012 |
| Creators | Gomes, Lenyta Oliveira |
| Contributors | Universidade Federal de Santa Catarina, Rae, Giles Alexander, Hara, Daniela Balz |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | 83 p.| il., grafs., tabs. |
| Source | reponame:Repositório Institucional da UFSC, instname:Universidade Federal de Santa Catarina, instacron:UFSC |
| Rights | info:eu-repo/semantics/openAccess |
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