Brasil
| Artigo
Effects of endothelin ETB receptor agonists and antagonists on the biphasic response in the ileum
Fecha
1999-03-19Registro en:
European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 369, n. 2, p. 205-213, 1999.
0014-2999
10.1016/S0014-2999(99)00062-X
WOS:000079347400009
Autor
Miasiro, N.
Karaki, H.
Matsuda, Y.
Paiva, ACM
Rae, G. A.
Institución
Resumen
In the guinea-pig ileum, both sarafotoxin S6c and IRL1620 (Suc-[Glu(9),Ala(11,15)]endothelin-1-(8-21) induced a concentration-dependent biphasic effect (relaxation and contraction), but distinct tachyphylaxis of the tissue. Cross-tachyphylaxis and additivity experiments evidenced distinct receptors for these agonists, BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]), an endothelin ETA receptor antagonist, did not affect the response induced by either agonist. PD145065 [Ac-(D-Bhg-Leu-Asp-Ile-Ile-Trp) (D-Bhg = SH-dibenzyl[a, d]cycloheptene-10,11-dihydroglycine)], an endothelin ETA/ETB receptor antagonist, inhibited the contractions induced by IRL1620 and sarafotoxin S6c in competitive and noncompetitive manner, respectively. RES-701-1 [cyclic(Gly(1)-Asp(9))(Gly-Asn-Trp-His-Gly-Thr-Ala-Pro-Phe-Asn-Tyr-Tyr-Trp)], an endothelin ETB1 receptor antagonist, inhibited both components of the response induced by LRL1620, whereas it inhibited mainly the relaxation induced by low sarafotoxin S6c doses. Apamin and suramin had different effects towards the agonists. Our results suggest that two endothelin ETB receptors with distinct signal transduction mechanism mediate the biphasic response: (1) the endothelin ETB1 receptor: sensitive to RES-701-1 and PD145065 and (2) the endothelin ETB2 receptor: less sensitive to RES-701-1 and PD145065. (C) 1999 Elsevier Science B.V. All rights reserved.