Low-temperature Modification of the Inhibitory Effects of Volatile Anesthetics on Airway Smooth Muscle Contraction in Dogs

2000 ◽  
Vol 93 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Michiaki Yamakage ◽  
Naoki Tsujiguchi ◽  
Jun-ichi Hattori ◽  
Yasuhiro Kamada ◽  
Akiyoshi Namiki

Background Because exposure to low temperature can modify the effect of volatile anesthetics on airway smooth muscle contraction, this study was conducted to investigate low-temperature modifications of the inhibitory effects of isoflurane and sevoflurane on canine tracheal smooth muscle tone by simultaneously measuring the muscle tension and intracellular concentration of Ca2+ ([Ca2+]i) and by measuring voltage-dependent Ca2+ channel activity. Methods [Ca2+]i was monitored by the 500-nm light emission ratio of preloaded fura-2, a Ca2+ indicator. Isometric tension was measured simultaneously. Whole cell patch clamp recording techniques were used to observe voltage-dependent Ca2+ channel activity in dispersed muscle cells. Isoflurane (0-3.0%) or sevoflurane (0-3%) was introduced to a bath solution at various temperatures (37, 34, or 31 degrees C). Results Low temperature (34 or 31 degrees C) reduced high-K+-induced (72.7 mm) muscle contraction and increased [Ca2+]i, but it enhanced carbachol-induced (1 microm) muscle contraction with a decrease in [Ca2+]i. The volatile anesthetics tested showed significant inhibition of both high-K+-induced and carbachol-induced airway smooth muscle contraction, with a concomitant decrease in [Ca2+]i. The inhibition of the carbachol-induced muscle contraction by volatile anesthetics was abolished partially by exposure to low temperature. Volatile anesthetics and low-temperature exposure significantly inhibited voltage-dependent Ca2+ channel activity of the smooth muscle. Conclusions Exposure of airway smooth muscle to low temperature leads to an increase in agonist-induced muscle contractility, with a decrease in [Ca2+]i. The inhibition of voltage-dependent Ca2+ channel activity by exposure to low temperature and by volatile anesthetics cam be attributed, at least in part, to the decrease in [Ca2+]i.

1995 ◽  
Vol 83 (6) ◽  
pp. 1274-1282 ◽  
Author(s):  
Michiaki Yamakage ◽  
Carol A. Hirshman ◽  
Thomas L. Croxton

Abstract Background Intravenously administered anesthetics directly inhibit airway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smooth muscle requires the influx of Calcium2+ through voltage-dependent Calcium2+ channels, it was hypothesized that intravenous anesthetics inhibit airway smooth muscle voltage-dependent Calcium2+ channels.


2001 ◽  
Vol 94 (4) ◽  
pp. 683-693 ◽  
Author(s):  
Michiaki Yamakage ◽  
Xiangdong Chen ◽  
Naoki Tsujiguchi ◽  
Yasuhiro Kamada ◽  
Akiyoshi Namiki

Background The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs). Methods Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution. Results The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle. Conclusions The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.


2006 ◽  
Vol 105 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Tetsuzo Nakayama ◽  
Alan R. Penheiter ◽  
Sumedha G. Penheiter ◽  
Eduardo N. Chini ◽  
Michael Thompson ◽  
...  

Background Halothane inhibits airway smooth muscle contraction in part by inhibiting the functional coupling between muscarinic receptors and one of its cognate heterotrimeric G proteins, Galphaq. Based on previous studies indicating a more potent effect of halothane and sevoflurane on airway smooth muscle contraction compared with isoflurane, the current study hypothesized that at anesthetic concentrations of 2 minimum alveolar concentration (MAC) or less, halothane and sevoflurane but not isoflurane inhibit acetylcholine-promoted Galphaq guanosine nucleotide exchange. Methods Galphaq guanosine nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the human M3 muscarinic receptor and human Galphaq. A radioactive, nonhydrolyzable analog of guanosine-5'-triphosphate, [35S]GTPgammaS, was used as a reporter for nucleotide exchange at Galphaq. Results Acetylcholine caused a concentration-dependent increase in Galphaq [35S]GTPgammaS-GDP exchange. Neither anesthetic affected constitutive Galphaq [35S]GTPgammaS-GDP exchange in the absence of acetylcholine. Conversely, each anesthetic caused a concentration-dependent and reversible inhibition of Galphaq [35S]GTPgammaS-GDP exchange when promoted by acetylcholine. At concentrations of 3 MAC or less, the effect of halothane and sevoflurane were significantly greater than that of isoflurane, with only a minimal inhibition by isoflurane observed at 2 MAC. Conclusion The differential effects of volatile anesthetics on acetylcholine-promoted guanosine nucleotide exchange at Galphaq are consistent with the apparent more potent direct effect of halothane and sevoflurane compared with isoflurane on muscarinic receptor-mediated contraction of isolated airway smooth muscle. These differential effects also suggest a mode of anesthetic action that could be due to anesthetic-protein interactions and not simply anesthetic accumulation in the lipid membrane.


2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Nana Wen ◽  
Lu Xue ◽  
Yongle Yang ◽  
Shunbo Shi ◽  
Qing-Hua Liu ◽  
...  

Abstract Background/Aims: Recently, effective and purified ingredients of traditional Chinese medicine (TCM) were extracted to play crucial roles in the treatment of pulmonary diseases. Our previous research focused on TCM drug screening aimed at abnormal airway muscle contraction during respiratory diseases. Coptisine, an effective ingredient extracted from bitter herbs has shown a series of antioxidant, antibacterial, cardioprotective and neuroprotective pharmacological properties. In the current study, we questioned whether coptisine could also participate in asthma treatment through relaxing abnormal contracted mouse airway smooth muscle (ASM). The present study aimed to characterize the relaxant effects of coptisine on mouse ASM and uncover the underlying molecular mechanisms. Methods: To investigate the role of coptisine on pre-contracted mouse ASM, a series of biological techniques, including force measurement and patch-clamp experiments were employed. Results: Coptisine was found to inhibit high K+ or acetylcholine chloride (ACh)-induced pre-contracted mouse tracheal rings in a dose-dependent manner. Further research demonstrated that the coptisine-induced mouse ASM relaxation was mediated by alteration of calcium mobilization via voltage-dependent L-type Ca2+ channels (VDLCCs) and non-selective cation channels (NSCCs). Conclusion: Our data showed that mouse ASM could be relaxed by coptisine via altering the intracellular Ca2+ concentration through blocking VDLCCs and NSCCs, which suggested that this pharmacological active constituent might be classified as a potential new drug for the treatment of abnormal airway muscle contraction.


1987 ◽  
Vol 79 (6) ◽  
pp. 899-908 ◽  
Author(s):  
T SHIMODA ◽  
J KRZANOWSKI ◽  
R LOCKEY ◽  
D MARTIN ◽  
M PEREZCRUET ◽  
...  

2004 ◽  
Vol 143 (4) ◽  
pp. 477-484 ◽  
Author(s):  
Dedmer Schaafsma ◽  
Reinoud Gosens ◽  
I Sophie T Bos ◽  
Herman Meurs ◽  
Johan Zaagsma ◽  
...  

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