Involvement of K+ channels in the relaxant effects of YC-1 in vascular smooth muscle

Sabine Seitz; Jörg W. Wegener; Johanna Rupp; Makino Watanabe; Andreas Jost; Rolf Gerhard; Asher Shainberg; Rikuo Ochi; Hermann Nawrath

doi:10.1016/s0014-2999(99)00574-9

Involvement of K⁺ channels in the relaxant effects of YC-1 in vascular smooth muscle

Sabine Seitz, Jörg W. Wegener, Johanna Rupp, Makino Watanabe, Andreas Jost, Rolf Gerhard, Asher Shainberg, Rikuo Ochi, Hermann Nawrath

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

This study addresses the question whether K⁺ channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 μM) more potently than those induced by K⁺(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 μM), and iberiotoxin (0.1 μM), but not glibenclamide (10 μM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 μM) induced a hyperpolarisation which was antagonised by 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 μM). In rat aorta, YC-1 (30 μM) increased the rate constant of ⁸⁶Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 μM), but inhibited by ODQ (50 μM) or charybdotoxin (0.2 μM). In smooth muscle cells from rat aorta, YC-1 (10 μM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K⁺ channels.

Original language	English
Pages (from-to)	11-18
Number of pages	8
Journal	European Journal of Pharmacology
Volume	382
Issue number	1
DOIs	https://doi.org/10.1016/s0014-2999(99)00574-9
State	Published - 1 Oct 1999

Bibliographical note

Funding Information:
We thank Dr. Schönafinger, Hoechst (Germany), for providing us with YC-1. This work was supported by grants (to H.N.) from the Deutsche Forschungsgemeinschaft (Germany) and the Umweltministerium of Rheinland-Pfalz (Germany).

Funding

We thank Dr. Schönafinger, Hoechst (Germany), for providing us with YC-1. This work was supported by grants (to H.N.) from the Deutsche Forschungsgemeinschaft (Germany) and the Umweltministerium of Rheinland-Pfalz (Germany).

Funders	Funder number
Umweltministerium of Rheinland-Pfalz
Deutsche Forschungsgemeinschaft

Keywords

BK(Ca) channel
Cyclic GMP
Guanylyl cyclase, soluble
Relaxation
Smooth muscle, vascular

Access to Document

10.1016/s0014-2999(99)00574-9

Cite this

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title = "Involvement of K+ channels in the relaxant effects of YC-1 in vascular smooth muscle",

abstract = "This study addresses the question whether K+ channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 μM) more potently than those induced by K+(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 μM), and iberiotoxin (0.1 μM), but not glibenclamide (10 μM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 μM) induced a hyperpolarisation which was antagonised by 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 μM). In rat aorta, YC-1 (30 μM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 μM), but inhibited by ODQ (50 μM) or charybdotoxin (0.2 μM). In smooth muscle cells from rat aorta, YC-1 (10 μM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K+ channels.",

keywords = "BK(Ca) channel, Cyclic GMP, Guanylyl cyclase, soluble, Relaxation, Smooth muscle, vascular",

author = "Sabine Seitz and Wegener, \{J{\"o}rg W.\} and Johanna Rupp and Makino Watanabe and Andreas Jost and Rolf Gerhard and Asher Shainberg and Rikuo Ochi and Hermann Nawrath",

note = "Funding Information: We thank Dr. Sch{\"o}nafinger, Hoechst (Germany), for providing us with YC-1. This work was supported by grants (to H.N.) from the Deutsche Forschungsgemeinschaft (Germany) and the Umweltministerium of Rheinland-Pfalz (Germany).",

year = "1999",

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doi = "10.1016/s0014-2999(99)00574-9",

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T1 - Involvement of K+ channels in the relaxant effects of YC-1 in vascular smooth muscle

AU - Seitz, Sabine

AU - Wegener, Jörg W.

AU - Rupp, Johanna

AU - Watanabe, Makino

AU - Jost, Andreas

AU - Gerhard, Rolf

AU - Shainberg, Asher

AU - Ochi, Rikuo

AU - Nawrath, Hermann

N1 - Funding Information: We thank Dr. Schönafinger, Hoechst (Germany), for providing us with YC-1. This work was supported by grants (to H.N.) from the Deutsche Forschungsgemeinschaft (Germany) and the Umweltministerium of Rheinland-Pfalz (Germany).

PY - 1999/10/1

Y1 - 1999/10/1

N2 - This study addresses the question whether K+ channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 μM) more potently than those induced by K+(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 μM), and iberiotoxin (0.1 μM), but not glibenclamide (10 μM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 μM) induced a hyperpolarisation which was antagonised by 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 μM). In rat aorta, YC-1 (30 μM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 μM), but inhibited by ODQ (50 μM) or charybdotoxin (0.2 μM). In smooth muscle cells from rat aorta, YC-1 (10 μM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K+ channels.

AB - This study addresses the question whether K+ channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 μM) more potently than those induced by K+(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 μM), and iberiotoxin (0.1 μM), but not glibenclamide (10 μM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 μM) induced a hyperpolarisation which was antagonised by 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 μM). In rat aorta, YC-1 (30 μM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 μM), but inhibited by ODQ (50 μM) or charybdotoxin (0.2 μM). In smooth muscle cells from rat aorta, YC-1 (10 μM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K+ channels.

KW - BK(Ca) channel

KW - Cyclic GMP

KW - Guanylyl cyclase, soluble

KW - Relaxation

KW - Smooth muscle, vascular

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SN - 0014-2999

VL - 382

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JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

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