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Modulation of human 5-hydroxytryptamine type 3AB receptors by volatile anesthetics and n-alcohols.
Stevens R
,
Rüsch D
,
Solt K
,
Raines DE
,
Davies PA
.
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Functional 5-hydroxytryptamine type 3 (5-HT3) receptors can be formed by 5-HT3A subunits alone or in combination with the 5-HT3B subunit, but only the 5-HT3A receptor has been previously studied with respect to the modulation by volatile anesthetics and n-alcohols. Using two-electrode voltage-clamp, we show for the first time the modulation of heteromeric human (h)5-HT3AB receptors, expressed in Xenopus oocytes, by a series of n-alcohols and halogenated volatile anesthetics. At twice their anesthetic concentration, compounds having a molecular volume of less than 110 A3 enhanced submaximal 5-HT-evoked current. Compounds larger than 110 A3 inhibited submaximal 5-HT-evoked current. In experiments examining 5-HT concentration-response relationships, chloroform and butanol caused a slight decrease in the 5-HT EC50. Sevoflurane and octanol inhibited 5-HT-evoked current at all 5-HT concentrations tested but had no effect upon the 5-HT EC50. Compared with previous data on homomeric h5-HT3A receptors, the presence of the h5-HT3B subunit reduces the enhancement of h5-HT3 receptors by smaller halogenated volatile anesthetics and n-alcohols. In summary, these results suggest that heteromeric h5-HT3AB receptors are modulated by halogenated volatile anesthetics at clinically relevant concentrations, in addition to n-alcohols, suggesting that these receptors may be another physiological target for these compounds. The modulation is dependent upon the molecular volume of the compound, further supporting the concept of an anesthetic binding pocket of limited volume common on other Cys-loop ligand-gated ion channels. Incorporation of the 5-HT3B subunit alters either the anesthetic binding site or the allosteric interactions between anesthetic binding and channel opening.
Alhaider,
Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA.
1991, Pubmed
Alhaider,
Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA.
1991,
Pubmed
Alifimoff,
Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.
1989,
Pubmed
Apfel,
Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design.
2002,
Pubmed
Campagna,
Mechanisms of actions of inhaled anesthetics.
2003,
Pubmed
Comet,
5-HT-mediated inhibition of cardiovagal baroreceptor reflex response during defense reaction in the rat.
2004,
Pubmed
Davies,
A novel class of ligand-gated ion channel is activated by Zn2+.
2003,
Pubmed
Davies,
The 5-HT3B subunit is a major determinant of serotonin-receptor function.
1999,
Pubmed
,
Xenbase
Deady,
Anesthetic potencies and the unitary theory of narcosis.
1981,
Pubmed
Dubin,
The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit.
1999,
Pubmed
,
Xenbase
Eger,
Women appear to have the same minimum alveolar concentration as men: a retrospective study.
2003,
Pubmed
Férézou,
5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons.
2002,
Pubmed
Hornby,
Central neurocircuitry associated with emesis.
2001,
Pubmed
Huang,
5-HT3A receptor subunits in the rat medial nucleus of the solitary tract: subcellular distribution and relation to the serotonin transporter.
2004,
Pubmed
Jenkins,
Evidence for a common binding cavity for three general anesthetics within the GABAA receptor.
2001,
Pubmed
Jenkins,
Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells.
1996,
Pubmed
Koshizaki,
5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons.
2003,
Pubmed
Koyama,
Presynaptic 5-HT3 receptor-mediated modulation of synaptic GABA release in the mechanically dissociated rat amygdala neurons.
2000,
Pubmed
Lopreato,
Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function.
2003,
Pubmed
,
Xenbase
Machu,
Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes.
1994,
Pubmed
,
Xenbase
McMahon,
Hippocampal interneurons are excited via serotonin-gated ion channels.
1997,
Pubmed
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Miller,
The pressure reversal of general anesthesia and the critical volume hypothesis.
1973,
Pubmed
Monk,
Generation of a selective 5-HT3B subunit-recognising polyclonal antibody; identification of immunoreactive cells in rat hippocampus.
2001,
Pubmed
Morales,
5-HT(3)-receptor subunits A and B are co-expressed in neurons of the dorsal root ganglion.
2001,
Pubmed
Morales,
Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system.
2002,
Pubmed
Niesler,
Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E.
2003,
Pubmed
Nosjean,
Serotonergic projections from the nodose ganglia to the nucleus tractus solitarius: an immunohistochemical and double labeling study in the rat.
1990,
Pubmed
Puig,
In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors.
2004,
Pubmed
Reeves,
The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review).
2002,
Pubmed
Stevens,
Molecular properties important for inhaled anesthetic action on human 5-HT3A receptors.
2005,
Pubmed
,
Xenbase
Stewart,
Introduction of the 5-HT3B subunit alters the functional properties of 5-HT3 receptors native to neuroblastoma cells.
2003,
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
Tanimoto,
The role of 5-hydroxytryptamine3 receptors in the vagal afferent activation-induced inhibition of the first cervical dorsal horn spinal neurons projected from tooth pulp in the rat.
2004,
Pubmed
Wadhwa,
Women have the same desflurane minimum alveolar concentration as men: a prospective study.
2003,
Pubmed
Wang,
Presynaptic 5-HT3 receptors evoke an excitatory response in dorsal vagal preganglionic neurones in anaesthetized rats.
1998,
Pubmed
Wood,
Short chain and long chain alkanols have different sites of action on nicotinic acetylcholine receptor channels from Torpedo.
1991,
Pubmed
Zhou,
Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex.
1999,
Pubmed
Zhou,
Pharmacologic characteristics of potentiation of 5-HT3 receptors by alcohols and diethyl ether in NCB-20 neuroblastoma cells.
1996,
Pubmed
