Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein

Masahiro Kamouchi, Z. Xiong, N. Teramoto, Shunichi Kajioka, K. Okabe, K. Kitamura

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

The effects of E4080 {(E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl) ethyl)-N'-methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl) phenyl)-3-butenamide dihydrochloride dihydrate} on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (I(Ca)), a transient outward current (I(TO)), a sustained outward current (I(SO)) and an oscillatory outward current (I(OO)), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (I(h)). When I(Ca) was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 μM E4080 increased and higher concentrations (10 μM) inhibited I(Ca), whereas, at the holding potential of -60 mV, E4080 (>1 μM) consistently inhibited I(Ca)), in a concentration-dependent manner. E4080 inhibited I(TO), I(SO) (≥1 μM) and I(h) (≥ 0.1 μM) concentration dependently. Inasmuch as 1 μM E4080 did not inhibit I(Ca) at the holding potential of -80 mV, the inhibition of I(TO) induced by 1 μM E4080 was not related to the inhibition of I(Ca). When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 μM) produced a maintained outward current (14.0 ± 15.3 pA), which was inhibited by glibenclamide. I(OO) was inhibited by E4080 (≥0.1 μM) and application of 1 μM glibenclamide partly restored I(OO). With single channel recording using the outside-out membrane patch, E4080 (≤1 μM) did not modify the activities of the large-conductance Ca-dependent K channels. These results indicate that E4080 has multiple actions on various ionic currents in the rabbit portal vein. The main factor contributing to the vasodilating action of E4080 in smooth muscle cells of rabbit portal vein is postulated from the electrical events to be closely related to reduction in cytosolic Ca.

元の言語英語
ページ(範囲)1396-1403
ページ数8
ジャーナルJournal of Pharmacology and Experimental Therapeutics
259
発行部数3
出版物ステータス出版済み - 12 1 1991

Fingerprint

Bradycardia
Portal Vein
Smooth Muscle Myocytes
Rabbits
Glyburide
Membranes
E 4080
Patch-Clamp Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

@article{097f2d632edc40fea3bce1c3d7474bb8,
title = "Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein",
abstract = "The effects of E4080 {(E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl) ethyl)-N'-methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl) phenyl)-3-butenamide dihydrochloride dihydrate} on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (I(Ca)), a transient outward current (I(TO)), a sustained outward current (I(SO)) and an oscillatory outward current (I(OO)), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (I(h)). When I(Ca) was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 μM E4080 increased and higher concentrations (10 μM) inhibited I(Ca), whereas, at the holding potential of -60 mV, E4080 (>1 μM) consistently inhibited I(Ca)), in a concentration-dependent manner. E4080 inhibited I(TO), I(SO) (≥1 μM) and I(h) (≥ 0.1 μM) concentration dependently. Inasmuch as 1 μM E4080 did not inhibit I(Ca) at the holding potential of -80 mV, the inhibition of I(TO) induced by 1 μM E4080 was not related to the inhibition of I(Ca). When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 μM) produced a maintained outward current (14.0 ± 15.3 pA), which was inhibited by glibenclamide. I(OO) was inhibited by E4080 (≥0.1 μM) and application of 1 μM glibenclamide partly restored I(OO). With single channel recording using the outside-out membrane patch, E4080 (≤1 μM) did not modify the activities of the large-conductance Ca-dependent K channels. These results indicate that E4080 has multiple actions on various ionic currents in the rabbit portal vein. The main factor contributing to the vasodilating action of E4080 in smooth muscle cells of rabbit portal vein is postulated from the electrical events to be closely related to reduction in cytosolic Ca.",
author = "Masahiro Kamouchi and Z. Xiong and N. Teramoto and Shunichi Kajioka and K. Okabe and K. Kitamura",
year = "1991",
month = "12",
day = "1",
language = "English",
volume = "259",
pages = "1396--1403",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Ionic currents involved in vasodilating actions of E4080, a newly synthesized bradycardia-inducing agent, in dispersed smooth muscle cells of the rabbit portal vein

AU - Kamouchi, Masahiro

AU - Xiong, Z.

AU - Teramoto, N.

AU - Kajioka, Shunichi

AU - Okabe, K.

AU - Kitamura, K.

PY - 1991/12/1

Y1 - 1991/12/1

N2 - The effects of E4080 {(E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl) ethyl)-N'-methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl) phenyl)-3-butenamide dihydrochloride dihydrate} on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (I(Ca)), a transient outward current (I(TO)), a sustained outward current (I(SO)) and an oscillatory outward current (I(OO)), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (I(h)). When I(Ca) was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 μM E4080 increased and higher concentrations (10 μM) inhibited I(Ca), whereas, at the holding potential of -60 mV, E4080 (>1 μM) consistently inhibited I(Ca)), in a concentration-dependent manner. E4080 inhibited I(TO), I(SO) (≥1 μM) and I(h) (≥ 0.1 μM) concentration dependently. Inasmuch as 1 μM E4080 did not inhibit I(Ca) at the holding potential of -80 mV, the inhibition of I(TO) induced by 1 μM E4080 was not related to the inhibition of I(Ca). When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 μM) produced a maintained outward current (14.0 ± 15.3 pA), which was inhibited by glibenclamide. I(OO) was inhibited by E4080 (≥0.1 μM) and application of 1 μM glibenclamide partly restored I(OO). With single channel recording using the outside-out membrane patch, E4080 (≤1 μM) did not modify the activities of the large-conductance Ca-dependent K channels. These results indicate that E4080 has multiple actions on various ionic currents in the rabbit portal vein. The main factor contributing to the vasodilating action of E4080 in smooth muscle cells of rabbit portal vein is postulated from the electrical events to be closely related to reduction in cytosolic Ca.

AB - The effects of E4080 {(E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl) ethyl)-N'-methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl) phenyl)-3-butenamide dihydrochloride dihydrate} on ionic currents recorded from the rabbit portal vein were investigated by using the patch-clamp technique. A depolarization of the membrane produced an inward Ca current (I(Ca)), a transient outward current (I(TO)), a sustained outward current (I(SO)) and an oscillatory outward current (I(OO)), whereas a hyperpolarization of the membrane produced a hyperpolarization-activated current (I(h)). When I(Ca) was evoked by a depolarizing pulse to 0 mV from the holding potential of -80 mV, 1 μM E4080 increased and higher concentrations (10 μM) inhibited I(Ca), whereas, at the holding potential of -60 mV, E4080 (>1 μM) consistently inhibited I(Ca)), in a concentration-dependent manner. E4080 inhibited I(TO), I(SO) (≥1 μM) and I(h) (≥ 0.1 μM) concentration dependently. Inasmuch as 1 μM E4080 did not inhibit I(Ca) at the holding potential of -80 mV, the inhibition of I(TO) induced by 1 μM E4080 was not related to the inhibition of I(Ca). When a continuous depolarization (0 mV) was applied to the cell, E4080 (1 μM) produced a maintained outward current (14.0 ± 15.3 pA), which was inhibited by glibenclamide. I(OO) was inhibited by E4080 (≥0.1 μM) and application of 1 μM glibenclamide partly restored I(OO). With single channel recording using the outside-out membrane patch, E4080 (≤1 μM) did not modify the activities of the large-conductance Ca-dependent K channels. These results indicate that E4080 has multiple actions on various ionic currents in the rabbit portal vein. The main factor contributing to the vasodilating action of E4080 in smooth muscle cells of rabbit portal vein is postulated from the electrical events to be closely related to reduction in cytosolic Ca.

UR - http://www.scopus.com/inward/record.url?scp=0026324139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026324139&partnerID=8YFLogxK

M3 - Article

C2 - 1762086

AN - SCOPUS:0026324139

VL - 259

SP - 1396

EP - 1403

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -