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Anesth Analg
2005 Jun 01;1006:1696-1703. doi: 10.1213/01.ANE.0000151720.36988.09.
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Molecular properties important for inhaled anesthetic action on human 5-HT3A receptors.
Stevens RJN
,
Rüsch D
,
Davies PA
,
Raines DE
.
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Although inhaled anesthetics have diverse effects on 5-hydroxytryptamine type 3 (5-HT3A) receptors, the mechanism accounting for this diversity is not understood. Studies have shown that modulation of 5-HT3A receptor currents by n-alcohols depends on molecular volume, suggesting that steric interactions between n-alcohols and their binding sites define their action on this receptor. Electrostatic interactions also play an important role in anesthetic action on other ligand-gated receptors. We aimed to determine the contribution of molecular volume and electrostatics in defining volatile anesthetic actions on 5-HT3A receptors. Human 5-HT3A receptors were expressed in, and recorded from, Xenopus oocytes using the two-electrode voltage-clamp technique. The effects of a range of volatile anesthetics, n-alcohols, and nonhalogenated alkanes on submaximal serotonin-evoked peak currents, and full serotonin concentration-response curves were defined. Volatile anesthetics and n-alcohols, but not alkanes, smaller than 0.120 nm3 enhanced submaximal serotonin-evoked peak currents whereas all larger agents reduced currents. Most compounds tested inhibited maximal serotonin-evoked peak currents to varying degrees. However, only agents smaller than 0.120 nm3 shifted the 5-HT3A receptor's serotonin concentration-response curve to the left, whereas larger anesthetics shifted them to the right. Modulation of human 5-HT3A-mediated currents by volatile anesthetics exhibits a dependence on molecular volume consistent with the n-alcohols, suggesting that both classes of agents may enhance 5-HT3A receptor function via the same mechanism. Furthermore, the enhancing but not inhibiting effects of anesthetic compounds on 5-HT3A receptor currents are modulated by electrostatic interactions.
Alifimoff,
Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.
1989, Pubmed
Alifimoff,
Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.
1989,
Pubmed
Deady,
Anesthetic potencies and the unitary theory of narcosis.
1981,
Pubmed
Eckenhoff,
Molecular interactions between inhaled anesthetics and proteins.
1997,
Pubmed
Eger,
Women appear to have the same minimum alveolar concentration as men: a retrospective study.
2003,
Pubmed
Firestone,
Actions of general anesthetics on acetylcholine receptor-rich membranes from Torpedo californica.
1986,
Pubmed
Jenkins,
Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells.
1996,
Pubmed
Lovinger,
Ethanol and trichloroethanol alter gating of 5-HT3 receptor-channels in NCB-20 neuroblastoma cells.
2000,
Pubmed
Machu,
Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes.
1994,
Pubmed
,
Xenbase
Nakahiro,
Potentiation of GABA-induced Cl- current by a series of n-alcohols disappears at a cutoff point of a longer-chain n-alcohol in rat dorsal root ganglion neurons.
1996,
Pubmed
Raines,
Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor.
1999,
Pubmed
Raines,
Nonhalogenated alkane anesthetics fail to potentiate agonist actions on two ligand-gated ion channels.
2001,
Pubmed
Raines,
The alkyl chain dependence of the effect of normal alcohols on agonist-induced nicotinic acetylcholine receptor desensitization kinetics.
1999,
Pubmed
Raines,
Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the effects on agonist enhancement, direct activation, and inhibition.
2003,
Pubmed
,
Xenbase
Reeves,
The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review).
2002,
Pubmed
Strum,
Partition coefficients for sevoflurane in human blood, saline, and olive oil.
1987,
Pubmed
Suzuki,
The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Wadhwa,
Women have the same desflurane minimum alveolar concentration as men: a prospective study.
2003,
Pubmed
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Wood,
Short chain and long chain alkanols have different sites of action on nicotinic acetylcholine receptor channels from Torpedo.
1991,
Pubmed
Wood,
Cycloalkanemethanols discriminate between volume- and length-dependent loss of activity of alkanols at the Torpedo nicotinic acetylcholine receptor.
1993,
Pubmed
Wu,
Ethanol stabilizes the open channel state of the Torpedo nicotinic acetylcholine receptor.
1994,
Pubmed
Zhou,
Pharmacologic characteristics of potentiation of 5-HT3 receptors by alcohols and diethyl ether in NCB-20 neuroblastoma cells.
1996,
Pubmed
Zuo,
Dual action of n-alcohols on neuronal nicotinic acetylcholine receptors.
2001,
Pubmed
