Effects of endothelin-3 on the isolated guinea-pig ileum: role of Na+ ions and endothelin receptor subtypes.
Endothelin-3 induced a relaxation followed by contraction in the isolated guinea-pig ileum. The contractile but not the relaxant component of the response was concentration-dependent in the dose range studied. Neuronal mechanisms, cyclic GMP and ATP-dependent K+ channels are not involved in the relaxing effect since this component was not affected by either tetrodotoxin, methylene blue or glibenclamide. Endothelin-3 induced tachyphylaxis (homologous desensitization) that was not fully reversed after a 3-h resting period. The responses were inhibited in low-Na+ medium or after treatment with ouabain. Verapamil affected both the relaxant and the contractile components of the response, and phorbol-12,13-dibutyrate affected mainly the contractile component. Cross-tachyphylaxis studies between endothelin-1 and endothelin-3 suggest the existence of at least two endothelin receptor subtypes (or different ligand-receptor complexes) in the guinea-pig ileum.
Miasiro
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Department of Biophysics, Escola Paulista de Medicina, São Paulo, Brazil.
Paiva
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AC
D000818:Animals; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D017466:Receptors, Endothelin; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D015240:Phorbol 12,13-Dibutyrate; D012964:Sodium; D014700:Verapamil