The Diverse Actions of Volatile and Gaseous Anesthetics on Human-cloned 5-Hydroxytryptamine3 Receptors Expressed in Xenopus Oocytes

  title={The Diverse Actions of Volatile and Gaseous Anesthetics on Human-cloned 5-Hydroxytryptamine3 Receptors Expressed in Xenopus Oocytes},
  author={Takahiro Suzuki and Hideki Koyama and Masahiro Sugimoto and Ichirō Uchida and Takashi Mashimo},
Background General anesthetics can modulate the 5-hydroxytryptamine type 3 (5-HT3) receptor, which may be involved in processes mediating nausea and vomiting, and peripheral nociception. The effects of the new volatile anesthetic sevoflurane and the gaseous anesthetics nitrous oxide (N2O) and xenon (Xe) on the 5-HT3 receptor have not been well-characterized. Methods Homomeric human-cloned 5-HT3A receptors were expressed in Xenopus oocytes. The effects of halothane, isoflurane, sevoflurane, N2O… 

Molecular Properties Important for Inhaled Anesthetic Action on Human 5-HT3A Receptors

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.

Molecular Actions of Propofol on Human 5-HT3A Receptors: Enhancement as Well as Inhibition by Closely Related Phenol Derivatives

At least two separate inhibitory actions on 5-HT3A receptors could be identified for propofol, whereas the enhancing action seen for the two related smaller phenol derivatives could no longer be detected.

Nitrous Oxide and Xenon Inhibit the Human (&agr;7)5 Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocyte

Results suggest that inhibition of the (&agr;7)5 nACh receptor by N2O and Xe may play a role in their anesthetic effects.

N-Methyl-d-Aspartate Receptor Channel Blocker–Like Discriminative Stimulus Effects of Nitrous Oxide Gas

The results support the hypothesis that the discriminative stimulus effects of N2O are at least partially mediated by NMDA antagonist effects similar to those produced by channel blockers, however, as none of the drugs tested fully mimicked the stimulus results of N 2O, other mechanisms may also be involved.

Xenon Acts by Inhibition of Non–N-methyl-d-aspartate Receptor–mediated Glutamatergic Neurotransmission in Caenorhabditis elegans

Xenon acts in Caenorhabditis elegans to alter locomotion through a mechanism requiring the non-NMDA glutamate receptor encoded by glr-1, unlike for the action of nitrous oxide in C. elegans, the NMDA receptors encoded by nmR-1 is not essential for sensitivity to xenon.

Molecular interactions between general anesthetics and the 5HT2B receptor

The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized and implicates the serotonergic GPCRs as potential anesthetic targets.



Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes.

  • T. MachuR. Harris
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1994
The results suggest that alcohols and volatile anesthetics have similar actions on 5-HT3 receptor function, which is in agreement with results of studies with other members of the superfamily of ligandgated ion channels.

Actions of general anaesthetics on 5‐HT3 receptors in N1E‐115 neuroblastoma cells

Inhibition of the 5‐HT3 receptor by the n‐alcohols exhibited a cutoff in potency similar to those previously found for tadpoles, luciferase enzymes and a neuronal nicotinic acetylcholine receptor channel.

A Transmembrane Site Determines Sensitivity of Neuronal Nicotinic Acetylcholine Receptors to General Anesthetics*

Examination of chimeric and point mutant rat nAChRs expressed in Xenopus oocytes identifies a single amino acid residue near the middle of the second transmembrane segment (TM2) that determines gaseous anesthetic sensitivity of nA ChRs, but these residues are not likely to be anesthetic-binding sites.

The 5-HT3B subunit is a major determinant of serotonin-receptor function

Surprisingly, the M2 region of the 5-HT3B subunit lacks any of the structural features that are known to promote the conductance of related receptors, and will be a valuable resource for defining the molecular mechanisms of ion-channel function.

Effects of general anaesthetics on ligand-gated ion channels.

There is no evidence for a substance related to the luciferases within the mammalian CNS to be identified and for the protein model of general anaesthesia to be advanced such a target site must be identified.

Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.

The data revealed that the 5-HT3R molecule has interspecies differences in both tissue distribution and functional profile, and the potency of the agonists to induce inward current paralleled that to compete with the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonists for mouse 5- HT3R, was a full agonist for human 5-ht3R.

Subunit-dependent Inhibition of Human Neuronal Nicotinic Acetylcholine Receptors and Other Ligand-gated Ion Channels by Dissociative Anesthetics Ketamine and Dizocilpine

Human nAChRs are inhibited by ketamine and dizocilpine at concentrations possibly achieved in vivo during anesthesia in a subunit-dependent manner, with &bgr; sub units being more critical than &agr; subunits.

How does xenon produce anaesthesia?

Although most general anaesthetics enhance the activity of inhibitory GABAA (γ-aminobutyric acid type-A) receptors, it is found that the effects of xenon on these receptors are negligible and xenon potently inhibits the excitatory NMDA (N-methyl-D-aspartate) receptor channels, which may account for many of Xenon's attractive pharmacological properties.