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Eur J Pharmacol
2008 Mar 17;5821-3:42-51. doi: 10.1016/j.ejphar.2007.12.023.
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Volatile anesthetics and endogenous cannabinoid anandamide have additive and independent inhibitory effects on alpha(7)-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes.
Jackson SN
,
Singhal SK
,
Woods AS
,
Morales M
,
Shippenberg T
,
Zhang L
,
Oz M
.
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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 microM) 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-HT(3) receptors comprised of the N-terminal domain of the alpha(7)-nicotinic acetylcholine receptor and the transmembrane and carboxyl-terminal domains of 5-HT(3) 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.
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