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

研究成果: 雜誌貢獻文章

25 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)750-759
頁數10
期刊Anesthesiology
91
發行號3
DOIs
出版狀態已發佈 - 九月 1999
對外發佈Yes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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    Lin, C. C., Shyr, M. H., Tan, P. P. C., Chien, C. S., Pan, S. L., Wang, C. C., Chiu, C. T., & Yang, C. M. (1999). Mechanisms underlying the inhibitory effect of propofol on the contraction of canine airway smooth muscle. Anesthesiology, 91(3), 750-759. https://doi.org/10.1097/00000542-199909000-00028