Effects of endothelin ETB receptor agonists and antagonists on the biphasic response in the ileum

Effects of endothelin ETB receptor agonists and antagonists on the biphasic response in the ileum

Author Miasiro, N. Google Scholar
Karaki, H. Google Scholar
Matsuda, Y. Google Scholar
Paiva, ACM Google Scholar
Rae, G. A. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Tokyo
Tokyo Res Labs
Universidade Federal de Santa Catarina (UFSC)
Abstract 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.
Keywords sarafotoxin S6c
IRL1620
ileum
guinea-pig
endothelin receptor subtype
tachyphylaxis
Language English
Date 1999-03-19
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 369, n. 2, p. 205-213, 1999.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 205-213
Origin http://dx.doi.org/10.1016/S0014-2999(99)00062-X
Access rights Closed access
Type Article
Web of Science ID WOS:000079347400009
URI http://repositorio.unifesp.br/handle/11600/26048

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