Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells

Toshiaki Sendo, Yoshinori Itoh, Keisei Aki, Michiko Oka, Ryozo Oishi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The effect of carbazochrome sodium sulfonate (AC-17), a hemostatic drug with capillary stabilising action, on the endothelial barrier dysfunction induced by a variety of vasoactive substances or agents that increase the vascular permeability was investigated in the monolayers of cultured porcine aortic endothelial cells (PAECs). The endothelial barrier function was determined by the transendothelial transport of albumin-conjugated Evans blue. AC-17 (0.1-1 M) reversed the barrier dysfunction induced by tryptase, thrombin and bradykinin without affecting the endothelial permeability enhanced by Ca2+ ionophores such as ionomycin and A23187 or phorbol 12-myristate 13-acetate. Immunofluorescence analysis showed that AC-17 reversed the tryptase-induced formation of actin stress fibres and disruption of VE-cadherin in PAECs. On the other hand, AC-17 (0.1-10 M) reduced concentration-dependently the enhancement of [3H]inositol triphosphate formation from [ 3H]myo-inositol induced by bradykinin and thrombin. Therefore, it is suggested that AC-17 reduces the vascular hyperpermeability induced by a variety of vasoactive agents through inhibition of agonist-induced phosphoinositide hydrolysis.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume368
Issue number3
DOIs
Publication statusPublished - Sep 1 2003
Externally publishedYes

Fingerprint

Phosphatidylinositols
Hydrolysis
Swine
Endothelial Cells
Tryptases
Bradykinin
Inositol
Thrombin
Capillary Action
Evans Blue
Stress Fibers
Ionomycin
Ionophores
Calcimycin
Capillary Permeability
Hemostatics
Fluorescent Antibody Technique
Blood Vessels
carbazochrome
Actins

Keywords

  • Bradykinin
  • Carbazochrome sodium sulfonate
  • Permeability
  • Phosphoinositide hydrolysis
  • Porcine aortic endothelial cells
  • Thrombin
  • Tryptase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells. / Sendo, Toshiaki; Itoh, Yoshinori; Aki, Keisei; Oka, Michiko; Oishi, Ryozo.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 368, No. 3, 01.09.2003, p. 175-180.

Research output: Contribution to journalArticle

@article{e43ead809d074d94a675d8e08694146d,
title = "Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells",
abstract = "The effect of carbazochrome sodium sulfonate (AC-17), a hemostatic drug with capillary stabilising action, on the endothelial barrier dysfunction induced by a variety of vasoactive substances or agents that increase the vascular permeability was investigated in the monolayers of cultured porcine aortic endothelial cells (PAECs). The endothelial barrier function was determined by the transendothelial transport of albumin-conjugated Evans blue. AC-17 (0.1-1 M) reversed the barrier dysfunction induced by tryptase, thrombin and bradykinin without affecting the endothelial permeability enhanced by Ca2+ ionophores such as ionomycin and A23187 or phorbol 12-myristate 13-acetate. Immunofluorescence analysis showed that AC-17 reversed the tryptase-induced formation of actin stress fibres and disruption of VE-cadherin in PAECs. On the other hand, AC-17 (0.1-10 M) reduced concentration-dependently the enhancement of [3H]inositol triphosphate formation from [ 3H]myo-inositol induced by bradykinin and thrombin. Therefore, it is suggested that AC-17 reduces the vascular hyperpermeability induced by a variety of vasoactive agents through inhibition of agonist-induced phosphoinositide hydrolysis.",
keywords = "Bradykinin, Carbazochrome sodium sulfonate, Permeability, Phosphoinositide hydrolysis, Porcine aortic endothelial cells, Thrombin, Tryptase",
author = "Toshiaki Sendo and Yoshinori Itoh and Keisei Aki and Michiko Oka and Ryozo Oishi",
year = "2003",
month = "9",
day = "1",
doi = "10.1007/s00210-003-0785-5",
language = "English",
volume = "368",
pages = "175--180",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells

AU - Sendo, Toshiaki

AU - Itoh, Yoshinori

AU - Aki, Keisei

AU - Oka, Michiko

AU - Oishi, Ryozo

PY - 2003/9/1

Y1 - 2003/9/1

N2 - The effect of carbazochrome sodium sulfonate (AC-17), a hemostatic drug with capillary stabilising action, on the endothelial barrier dysfunction induced by a variety of vasoactive substances or agents that increase the vascular permeability was investigated in the monolayers of cultured porcine aortic endothelial cells (PAECs). The endothelial barrier function was determined by the transendothelial transport of albumin-conjugated Evans blue. AC-17 (0.1-1 M) reversed the barrier dysfunction induced by tryptase, thrombin and bradykinin without affecting the endothelial permeability enhanced by Ca2+ ionophores such as ionomycin and A23187 or phorbol 12-myristate 13-acetate. Immunofluorescence analysis showed that AC-17 reversed the tryptase-induced formation of actin stress fibres and disruption of VE-cadherin in PAECs. On the other hand, AC-17 (0.1-10 M) reduced concentration-dependently the enhancement of [3H]inositol triphosphate formation from [ 3H]myo-inositol induced by bradykinin and thrombin. Therefore, it is suggested that AC-17 reduces the vascular hyperpermeability induced by a variety of vasoactive agents through inhibition of agonist-induced phosphoinositide hydrolysis.

AB - The effect of carbazochrome sodium sulfonate (AC-17), a hemostatic drug with capillary stabilising action, on the endothelial barrier dysfunction induced by a variety of vasoactive substances or agents that increase the vascular permeability was investigated in the monolayers of cultured porcine aortic endothelial cells (PAECs). The endothelial barrier function was determined by the transendothelial transport of albumin-conjugated Evans blue. AC-17 (0.1-1 M) reversed the barrier dysfunction induced by tryptase, thrombin and bradykinin without affecting the endothelial permeability enhanced by Ca2+ ionophores such as ionomycin and A23187 or phorbol 12-myristate 13-acetate. Immunofluorescence analysis showed that AC-17 reversed the tryptase-induced formation of actin stress fibres and disruption of VE-cadherin in PAECs. On the other hand, AC-17 (0.1-10 M) reduced concentration-dependently the enhancement of [3H]inositol triphosphate formation from [ 3H]myo-inositol induced by bradykinin and thrombin. Therefore, it is suggested that AC-17 reduces the vascular hyperpermeability induced by a variety of vasoactive agents through inhibition of agonist-induced phosphoinositide hydrolysis.

KW - Bradykinin

KW - Carbazochrome sodium sulfonate

KW - Permeability

KW - Phosphoinositide hydrolysis

KW - Porcine aortic endothelial cells

KW - Thrombin

KW - Tryptase

UR - http://www.scopus.com/inward/record.url?scp=0141958896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141958896&partnerID=8YFLogxK

U2 - 10.1007/s00210-003-0785-5

DO - 10.1007/s00210-003-0785-5

M3 - Article

C2 - 12928765

AN - SCOPUS:0141958896

VL - 368

SP - 175

EP - 180

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 3

ER -