Volatile anesthetics and endogenous cannabinoid anandamide have additive and independent inhibitory effects on α7-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes

被引:13
|
作者
Jackson, Shelley N.
Singhal, Sachin K. [2 ]
Woods, Arnina S.
Morales, Marisela
Shippenberg, Toni [1 ]
Zhang, Li [2 ]
Oz, Murat [1 ]
机构
[1] NIDA, NIH, DHHS, Intramural Res Program,Integrat Neurosci Sect,Cel, Baltimore, MD 21224 USA
[2] NIAAA, NIH, DHHS, Lab Integrat Neurosci, Rockville, MD 20852 USA
关键词
anandamide; volatile anesthetic; nicotinic receptor; Xenopus oocyte;
D O I
10.1016/j.ejphar.2007.12.023
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In earlier studies, the volatile anesthetics and the endogenous cannabinoid anandamide have been shown to inhibit the function of alpha(7)-nicotinic acetylcholine receptors. In the present study, interactions between the effects of volatile anesthetics and anandamide on the function of alpha(7)-nicotinic acetylcholine receptors expressed in Xenopus oocytes were investigated using the two-electrode voltage-clamp technique. Anandamide and volatile anesthetics isoflurane and halothane inhibited currents evoked with acetylcholine (100 mu M) in a reversible and concentration-dependent manner. Coapplication of anandamide and volatile anesthetics caused a significantly greater inhibition of alpha(7)-nicotinic acetylcholine receptor function than anandamide or volatile anesthetics alone. Analyses of oocytes by matrix-assisted laser desorption/ionization mass spectroscopy indicated that volatile anesthetics did not alter the lipid profile of oocytes. Results of studies with chimeric alpha(7)-nicotinic acetylcholine-5-HT3 receptors comprised of the N-terminal domain of the alpha(7)-nicotinic acetylcholine receptor and the transmembrane and carboxyl-terminal domains of 5-HT3 receptors suggest that while isoflurane inhibition of the alpha(7)-nicotinic acetylcholine receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide involves transmembrane and carboxyl-terminal domains of the receptors. These data indicate that endocannabinoids and isoflurane have additive inhibitory effects on alpha(7)-nicotinic acetylcholine receptor function through allosteric binding sites located on the distinct regions of the receptor. Published by Elsevier B.V.
引用
收藏
页码:42 / 51
页数:10
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