Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells

X. Y. Yu, W. Hubbard, Ernst W Spannhake

Research output: Contribution to journalArticle

Abstract

To determine the effect of mediators released from cultured canine bronchial epithelial cells on contraction of canine tracheal smooth muscle, we treated smooth muscle strips with piperazine-N,N'-bis(2-ethanesulfonic acid) buffer 'conditioned' by 5 h incubation with cultures of 4- to 5-day-old cultured epithelial cells. Pretreatment of tracheal smooth muscle with conditioned buffer for 5 min resulted in a significant shift to the right of the contractile dose-response curve to histamine in the range of 10-8 to 5 x 10-4 M. In addition, conditioned buffer induced a dose-related relaxation of the muscle precontracted by histamine (5 μM). Relaxant activity was also evident against tissues precontracted by 5-hydroxytryptamine or methacholine. Lipid extraction of conditioned buffer reduced its activity to that of the fresh buffer control. Prior treatment of the cells in culture with the cyclooxygenase inhibitor, sodium meclofenamate (4 μM), markedly reduced the relaxant effect of the conditioned buffer, whereas prior treatment with MK- 886, an inhibitor of 5-lipoxygenase, did not alter relaxant activity. Analysis of prostanoids released into the buffer by epithelial cells indicated the presence of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F(1α), the former in concentrations sufficient to account for the effect of conditioned buffer on precontracted tracheal muscle. Prostaglandin I2 appeared to have a synergistic effect on PGE2-induced relaxation. We conclude that canine bronchial epithelial cells exhibit baseline release of a relaxant lipid factor(s) that can both inhibit and reverse the contraction of tracheal smooth muscle by histamine. The data suggest that PGE2 is the mediator principally responsible for this relaxant activity released spontaneously by bronchial epithelial cells in culture.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume262
Issue number2 6-2
StatePublished - 1992

Fingerprint

Smooth Muscle
Canidae
Buffers
Epithelial Cells
Dinoprostone
Histamine
L 663536
Cell Culture Techniques
Meclofenamic Acid
Lipids
Lipoxygenase Inhibitors
Muscle Relaxation
Cyclooxygenase Inhibitors
Methacholine Chloride
Epoprostenol
Prostaglandins
Cultured Cells
Serotonin
Muscles

Keywords

  • 5- lipoxygenase inhibitor
  • 5-hydroxytryptamine
  • airways
  • bronchodilation
  • cell culture
  • cyclooxygenase inhibitor
  • epithelium-derived relaxing factor
  • histamine
  • methacholine
  • pharmacology
  • prostaglandin E
  • prostaglandin I
  • relaxation
  • tissue bath

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

@article{9bf5bd1deb044880bd20b16630da361d,
title = "Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells",
abstract = "To determine the effect of mediators released from cultured canine bronchial epithelial cells on contraction of canine tracheal smooth muscle, we treated smooth muscle strips with piperazine-N,N'-bis(2-ethanesulfonic acid) buffer 'conditioned' by 5 h incubation with cultures of 4- to 5-day-old cultured epithelial cells. Pretreatment of tracheal smooth muscle with conditioned buffer for 5 min resulted in a significant shift to the right of the contractile dose-response curve to histamine in the range of 10-8 to 5 x 10-4 M. In addition, conditioned buffer induced a dose-related relaxation of the muscle precontracted by histamine (5 μM). Relaxant activity was also evident against tissues precontracted by 5-hydroxytryptamine or methacholine. Lipid extraction of conditioned buffer reduced its activity to that of the fresh buffer control. Prior treatment of the cells in culture with the cyclooxygenase inhibitor, sodium meclofenamate (4 μM), markedly reduced the relaxant effect of the conditioned buffer, whereas prior treatment with MK- 886, an inhibitor of 5-lipoxygenase, did not alter relaxant activity. Analysis of prostanoids released into the buffer by epithelial cells indicated the presence of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F(1α), the former in concentrations sufficient to account for the effect of conditioned buffer on precontracted tracheal muscle. Prostaglandin I2 appeared to have a synergistic effect on PGE2-induced relaxation. We conclude that canine bronchial epithelial cells exhibit baseline release of a relaxant lipid factor(s) that can both inhibit and reverse the contraction of tracheal smooth muscle by histamine. The data suggest that PGE2 is the mediator principally responsible for this relaxant activity released spontaneously by bronchial epithelial cells in culture.",
keywords = "5- lipoxygenase inhibitor, 5-hydroxytryptamine, airways, bronchodilation, cell culture, cyclooxygenase inhibitor, epithelium-derived relaxing factor, histamine, methacholine, pharmacology, prostaglandin E, prostaglandin I, relaxation, tissue bath",
author = "Yu, {X. Y.} and W. Hubbard and Spannhake, {Ernst W}",
year = "1992",
language = "English (US)",
volume = "262",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2 6-2",

}

TY - JOUR

T1 - Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells

AU - Yu, X. Y.

AU - Hubbard, W.

AU - Spannhake, Ernst W

PY - 1992

Y1 - 1992

N2 - To determine the effect of mediators released from cultured canine bronchial epithelial cells on contraction of canine tracheal smooth muscle, we treated smooth muscle strips with piperazine-N,N'-bis(2-ethanesulfonic acid) buffer 'conditioned' by 5 h incubation with cultures of 4- to 5-day-old cultured epithelial cells. Pretreatment of tracheal smooth muscle with conditioned buffer for 5 min resulted in a significant shift to the right of the contractile dose-response curve to histamine in the range of 10-8 to 5 x 10-4 M. In addition, conditioned buffer induced a dose-related relaxation of the muscle precontracted by histamine (5 μM). Relaxant activity was also evident against tissues precontracted by 5-hydroxytryptamine or methacholine. Lipid extraction of conditioned buffer reduced its activity to that of the fresh buffer control. Prior treatment of the cells in culture with the cyclooxygenase inhibitor, sodium meclofenamate (4 μM), markedly reduced the relaxant effect of the conditioned buffer, whereas prior treatment with MK- 886, an inhibitor of 5-lipoxygenase, did not alter relaxant activity. Analysis of prostanoids released into the buffer by epithelial cells indicated the presence of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F(1α), the former in concentrations sufficient to account for the effect of conditioned buffer on precontracted tracheal muscle. Prostaglandin I2 appeared to have a synergistic effect on PGE2-induced relaxation. We conclude that canine bronchial epithelial cells exhibit baseline release of a relaxant lipid factor(s) that can both inhibit and reverse the contraction of tracheal smooth muscle by histamine. The data suggest that PGE2 is the mediator principally responsible for this relaxant activity released spontaneously by bronchial epithelial cells in culture.

AB - To determine the effect of mediators released from cultured canine bronchial epithelial cells on contraction of canine tracheal smooth muscle, we treated smooth muscle strips with piperazine-N,N'-bis(2-ethanesulfonic acid) buffer 'conditioned' by 5 h incubation with cultures of 4- to 5-day-old cultured epithelial cells. Pretreatment of tracheal smooth muscle with conditioned buffer for 5 min resulted in a significant shift to the right of the contractile dose-response curve to histamine in the range of 10-8 to 5 x 10-4 M. In addition, conditioned buffer induced a dose-related relaxation of the muscle precontracted by histamine (5 μM). Relaxant activity was also evident against tissues precontracted by 5-hydroxytryptamine or methacholine. Lipid extraction of conditioned buffer reduced its activity to that of the fresh buffer control. Prior treatment of the cells in culture with the cyclooxygenase inhibitor, sodium meclofenamate (4 μM), markedly reduced the relaxant effect of the conditioned buffer, whereas prior treatment with MK- 886, an inhibitor of 5-lipoxygenase, did not alter relaxant activity. Analysis of prostanoids released into the buffer by epithelial cells indicated the presence of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F(1α), the former in concentrations sufficient to account for the effect of conditioned buffer on precontracted tracheal muscle. Prostaglandin I2 appeared to have a synergistic effect on PGE2-induced relaxation. We conclude that canine bronchial epithelial cells exhibit baseline release of a relaxant lipid factor(s) that can both inhibit and reverse the contraction of tracheal smooth muscle by histamine. The data suggest that PGE2 is the mediator principally responsible for this relaxant activity released spontaneously by bronchial epithelial cells in culture.

KW - 5- lipoxygenase inhibitor

KW - 5-hydroxytryptamine

KW - airways

KW - bronchodilation

KW - cell culture

KW - cyclooxygenase inhibitor

KW - epithelium-derived relaxing factor

KW - histamine

KW - methacholine

KW - pharmacology

KW - prostaglandin E

KW - prostaglandin I

KW - relaxation

KW - tissue bath

UR - http://www.scopus.com/inward/record.url?scp=0026594564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026594564&partnerID=8YFLogxK

M3 - Article

C2 - 1539679

AN - SCOPUS:0026594564

VL - 262

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 2 6-2

ER -