Halothane Inhibits Signaling through m1 Muscarinic Receptors Expressed in Xenopus Oocytes
Halothane Inhibits Signaling through m1 Muscarinic Receptors Expressed in Xenopus Oocytes
复制标题
氟烷通过爪蟾卵母细胞中表达的 m1 毒蕈碱受体抑制信号传导
DOI：
10.1097/00000542-199501000-00022
复制
发表时间：
1995
期刊：
影响因子：
8.8
通讯作者：
M. Durieux
中科院分区：
文献类型：
--
作者：
M. Durieux
背景：研究挥发性麻醉药与M胆碱受体之间的相互作用主要是通过结合分析或在来源于组织或细胞的功能系统中进行的，这些系统通常包含多种受体亚型。由于与M受体信号系统的相互作用可以解释麻醉药的某些作用和副作用，并形成麻醉剂-蛋白质相互作用的一般模型，因此作者在一个孤立的系统中研究了麻醉对M受体信号的抑制。方法体外制备M_1受体亚型基因，并在非洲爪哇卵母细胞中表达。测定氟烷对甲基胆碱诱导的细胞内钙离子释放的影响。血管紧张素II受体的表达用于评估麻醉对细胞内信号转导的影响。结果卵母细胞表达的M1受体具有功能性，且可被阿托品和哌仑西平所抑制。氟烷以剂量依赖的方式抑制M1毒碱信号转导：0.3 mM氟烷对10 sup~(-7)M甲基胆碱的抑制作用为一半。这种作用是可逆的，并可被高浓度的毒扁豆碱激动剂所克服。0.34 mM氟烷对血管紧张素II信号转导无影响。结论氟烷可抑制M1毒鼠碱信号转导，而氟烷对血管紧张素信号转导无影响，提示非洲爪哇卵母细胞内信号转导系统未受影响。因此，氟烷最有可能的作用部位是受体和/或G蛋白。卵母细胞为详细研究麻醉剂-蛋白质相互作用的分子机制提供了一个通用的系统。
Background Interactions between volatile anesthetics and muscarinic acetylcholine receptors have been studied primarily in binding assays or in functional systems derived from tissues or cells, often containing multiple receptor subtypes. Because interactions with muscarinic signaling systems may explain some effects and side effects of anesthetics and form a model for anesthetic‐protein interactions in general, the author studied anesthetic inhibition of muscarinic signaling in an isolated system. Methods mRNA encoding the m1 muscarinic receptor subtype was prepared in vitro and expressed in Xenopus oocytes. Effects of halothane on methylcholine‐induced intracellular Calcium2+ release was measured. Angiotensin II receptors were expressed to evaluate anesthetic effects on intracellular signaling. Results m1 Receptors expressed in oocytes were functional, and could be inhibited by atropine and pirenzepine. Halothane depressed m1 muscarinic signaling in a dose‐dependent manner: half‐maximal inhibition of 10 sup ‐7 M methylcholine was obtained with 0.3 mM halothane. The effect was reversible and could be overcome by high concentrations of muscarinic agonist. Angiotensin II signaling was unaffected by 0.34 mM halothane. Conclusions m1 Muscarinic signaling is inhibited by halothane, and lack of halothane effect on angiotensin signaling indicates that the intracellular signaling systems of Xenopus oocytes are unaffected. Therefore, the most likely site of halothane action is the receptor and/or G protein. Oocytes provide a versatile system for detailed investigation into the molecular mechanism of anesthetic‐protein interactions.
登录
查看更多内容
氟烷减弱大鼠心脏腺苷酸环化酶的毒蕈碱抑制作用。
影响因子：
5.8
作者：
Narayanan,TK;Confer,RA;DennisonJr,RL;Anthony,BL;Aronstam,RS
通讯作者：
Aronstam,RS
安氟烷抑制小鼠和人脑爪蟾卵母细胞中表达的磷脂酰肌醇连接的乙酰胆碱和血清素受体的功能。
影响因子：
3.6
作者：
Lin,LH;Leonard,S;Harris,RA
通讯作者：
Harris,RA
在爪蟾卵母细胞中研究的巴比妥类药物可抑制通过人脑钙通道的电流。
DOI：
--
发表时间：
1988
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Gundersen,CB;Umbach,JA;Swartz,BE
通讯作者：
Swartz,BE
挥发性麻醉剂对腺苷酸环化酶活性的毒蕈碱调节的影响。
影响因子：
5.8
作者：
Anthony,BL;Dennison,RL;Aronstam,RS
通讯作者：
Aronstam,RS
对毒蕈碱信号转导的麻醉作用。
影响因子：
0.6
作者：
Aronstam,RS;DennisonJr,RL
通讯作者：
DennisonJr,RL