Volatile anesthetics and endogenous cannabinoid anandamide have additive and independent inhibitory effects on alpha(7)-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes.
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.
Jackson
Shelley N
SN
National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Singhal
Sachin K
SK
Woods
Amina S
AS
Morales
Marisela
M
Shippenberg
Toni
T
Zhang
Li
L
Oz
Murat
M
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D063388:Endocannabinoids; D005260:Female; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018685:Anesthetics, Inhalation; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018733:Nicotinic Antagonists; D053284:Polyunsaturated Alkamides; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D007530:Isoflurane; D006221:Halothane; C078814:anandamide