Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle

Chih Chung Lin, Ming Hwang Shyr, P. P C Tan, Chin Sung Chien, Shiow L. Pan, Chuan Chwan Wang, Chi T. Chiu, Chuen M. Yang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear. Methods: Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay. Results: Pretreatment with propofol shifts the concentration response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 μM propofol but was significantly increased by 300 μM (propofol, 952 ± 229 pM; control, 588 ± 98 pM; P <0.05). Conclusions: Propofol attenuates the muscarinic receptor-mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+ mobilization through the inhibition of the receptor-coupled signal-transduction pathway.

Original languageEnglish
Pages (from-to)750-759
Number of pages10
JournalAnesthesiology
Volume91
Issue number3
DOIs
Publication statusPublished - Sep 1999
Externally publishedYes

Fingerprint

Propofol
Smooth Muscle
Canidae
Carbachol
Inositol Phosphates
Muscarinic Receptors
Muscle Contraction
Calcium
Scopolamine Hydrobromide
Fura-2
Phosphatidylinositols
Smooth Muscle Myocytes
Signal Transduction
Hydrolysis

Keywords

  • Anesthetics
  • Ca
  • Contraction
  • Fura-2
  • Inositol phosphates
  • Propofol

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle. / Lin, Chih Chung; Shyr, Ming Hwang; Tan, P. P C; Chien, Chin Sung; Pan, Shiow L.; Wang, Chuan Chwan; Chiu, Chi T.; Yang, Chuen M.

In: Anesthesiology, Vol. 91, No. 3, 09.1999, p. 750-759.

Research output: Contribution to journalArticle

Lin, Chih Chung ; Shyr, Ming Hwang ; Tan, P. P C ; Chien, Chin Sung ; Pan, Shiow L. ; Wang, Chuan Chwan ; Chiu, Chi T. ; Yang, Chuen M. / Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle. In: Anesthesiology. 1999 ; Vol. 91, No. 3. pp. 750-759.
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abstract = "Background: Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear. Methods: Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay. Results: Pretreatment with propofol shifts the concentration response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 μM propofol but was significantly increased by 300 μM (propofol, 952 ± 229 pM; control, 588 ± 98 pM; P <0.05). Conclusions: Propofol attenuates the muscarinic receptor-mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+ mobilization through the inhibition of the receptor-coupled signal-transduction pathway.",
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AU - Lin, Chih Chung

AU - Shyr, Ming Hwang

AU - Tan, P. P C

AU - Chien, Chin Sung

AU - Pan, Shiow L.

AU - Wang, Chuan Chwan

AU - Chiu, Chi T.

AU - Yang, Chuen M.

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N2 - Background: Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear. Methods: Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay. Results: Pretreatment with propofol shifts the concentration response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 μM propofol but was significantly increased by 300 μM (propofol, 952 ± 229 pM; control, 588 ± 98 pM; P <0.05). Conclusions: Propofol attenuates the muscarinic receptor-mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+ mobilization through the inhibition of the receptor-coupled signal-transduction pathway.

AB - Background: Propofol has been shown to produce relaxation of preconstricted airway smooth muscle. Although the inhibition of calcium mobilization is supposed to be the major mechanism of action, the whole picture of the mechanisms is not completely clear. Methods: Contractile response was performed using canine tracheal rings. The effects of propofol on carbachol-induced mobilization of intracellular Ca2+ and phosphoinositide hydrolysis were measured using cultured canine tracheal smooth muscle cells by monitoring fura-2 signal and assessing the accumulation of [3H]-inositol phosphates. To detect the effect of propofol on muscarinic receptor density and affinity, [3H]N-methyl-scopolamine was used as a radioligand for receptor binding assay. Results: Pretreatment with propofol shifts the concentration response curves of carbachol-induced smooth muscle contraction to the right in a concentration-dependent manner without changing the maximal response. Propofol not only decreased the release of Ca2+ from internal stores but also inhibited the calcium influx induced by carbachol. In addition, carbachol-induced inositol phosphate accumulation was attenuated by propofol; the inhibitory pattern was similar to the contractile response. Moreover, propofol did not alter the density of muscarinic receptors. The dissociation constant value was not altered by pretreatment with 100 μM propofol but was significantly increased by 300 μM (propofol, 952 ± 229 pM; control, 588 ± 98 pM; P <0.05). Conclusions: Propofol attenuates the muscarinic receptor-mediated airway muscle contraction. The mechanism underlying these effects was attenuation of inositol phosphate generation and inhibition of Ca2+ mobilization through the inhibition of the receptor-coupled signal-transduction pathway.

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KW - Inositol phosphates

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