Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas. Programa de Pós-graduação em Farmacologia. / Made available in DSpace on 2012-10-23T17:59:18Z (GMT). No. of bitstreams: 1
248609.pdf: 584796 bytes, checksum: 8cfe067ea80cee93cf54684419c059c3 (MD5) / The nociceptive effects of Endothelin-1 (ET) are well-known. This peptide is synthesized by cleavage of Big ET-1 by Endothelin Converting Enzyme (ECE), however, Big ET-1 can be also cleaved by mast cell-derived chymase to ET-1(1-31), which can be converted to ET-1 by the enzyme neutral endopeptidase-24.11 (NEP). The present study aimed to assess, pharmacologically, the ability of ET-1(1-31) to induce nociception and mechanical hypernociception in the hind paw of mice and compare its effects with those evoked by ET-1 and Big ET-1. The intra-plantar (i.pl) injection of ET-1 (3 to 30 pmol), ET-1(1-31) (30 to 100 pmol) or Big ET-1 (30 to 100 pmol) induced dose-dependent nociception and hypernociception. Local pretreatment of the animals with thiorphan (NEP inhibitor, 300 nmol, i.pl.) or phosphoramidon (NEP and ECE inhibitors, 100 nmol, i.pl.), reduced nociception induced by ET-1(1-31) (10 pmol) or by ET-1(1-31) and Big ET-1 (30 pmol), respectively. On the other hand, pre treatment with chymostatin (chymase inhibitor, 100 nmol) did not alter the nociception induced by ET-1, ET-1 (1-31) or Big ET-1. Mast cell degranulation by i.pl. injection of compound 48/80 (0.05 to 1 ìg) or OVA (0.05 to 1 ìg) also evoked nociception and mechanical hypernociception. The association of Big ET-1 (30 pmol) with sub-effective doses of compound 48/80 (0.1 ìg) or OVA (0.05 ìg) resulted in potentiation of Big-ET-1-induced nociception by 93.5% e 154%, respectively. Pre-treatment with phosphoramidon (100 nmol) or chymostatin (100 nmol) reduced the nociception induced by Big ET-1 associated with compound 48/80 or OVA, while thiorphan was only able to reduce the nociception induced by the association of Big ET-1 plus compound 48/80 at 1000 nmol. Nociception induced by compound 48/80 (1.0 ìg) and OVA (0.3 ìg) was reduced by pretreatment with phosphoramidon or chymostatin or BQ-123 (selective ETBAB receptor antagonist, 10 nmol), while BQ-788 (selective ETBBB receptor antagonist, 10 nmol) and thiorphan (1000 nmol) reduced only nociception induced by OVA and compound 48/80, respectively. The results of the current study suggest that ET-1, formed via an alternative synthesis pathway, which involves formation of the intermediary peptide ET-1(1-31), contributes significantly to nociception induced by the activation of mast cells.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufsc.br:123456789/91030 |
| Date | January 2008 |
| Creators | Somensi, Amélia Regina |
| Contributors | Universidade Federal de Santa Catarina, Rae, Giles Alexander |
| Publisher | Florianópolis, SC |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | vi, 93 f.| il., grafs. |
| Source | reponame:Repositório Institucional da UFSC, instname:Universidade Federal de Santa Catarina, instacron:UFSC |
| Rights | info:eu-repo/semantics/openAccess |
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