2 RECEPTOR SUBTYPES ARE INVOLVED in the CONTRACTILE COMPONENT of the GUINEA-PIG ILEUM RESPONSES TO ENDOTHELINS

• Autor(a) principal: Miasiro, N. [UNIFESP]
• Data de Publicação: 1993
• Outros Autores: Paiva, ACM [UNIFESP], Ihara, M., Yano, M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1097/00005344-199322008-00057; http://repositorio.unifesp.br/handle/11600/25294
• topic: ENDOTHELIN-1; ENDOTHELIN-3; RECEPTOR SUBTYPES; ENDOTHELIN ANTAGONIST; TACHYPHYLAXIS

Endothelin-I (ET-1) and endothelin-3 (ET-3) induced a biphasic response (relaxation and contraction) in the guinea pig ileum. Short-term activation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) inhibited the contractile but not the relaxing component of the responses, as did H-7. Long-term pretreatment with PDBu reversed the short-term inhibition but did not affect the tachyphylaxis induced by ET-1. These results suggest that PKC contributes to ET-1 contraction but not to tachyphylaxis. the ETA antagonist BQ- 123, at 34 nM, competitively inhibited ET-1 contraction, but at 340 nM the inhibition was noncompetitive. Dose-response curves for ET-1 relaxation were shifted to the left. for ET-3, BQ-123 (340 nM) only decreased the maximal contractile response of the dose-response curve without affecting the relaxation. We suggest that in this tissue there is one receptor for ET-1-induced contraction, which is competitively antagonized by BQ-123, and another one for ET-3-induced contraction, which is noncompetitively antagonized by BQ-123.