Korean J Anesthesiol.  1999 Aug;37(2):295-302. 10.4097/kjae.1999.37.2.295.

Inhibitory Effects of Structurally Different Neuromuscular Blockers on the Serotonin Type 3 Receptor Expressed in Xenopus Oocytes

• Min KT
• Nam YT
• Oh KM
• Yang J

• KMID: 2237018
• DOI: http://doi.org/10.4097/kjae.1999.37.2.295

Abstract

BACKGROUND: The serotonin type 3 receptors are diffusely distributed in both the central and the peripheral nervous system. Physiological and pathophysiological processes thought to be mediated by this receptor include nausea and vomiting, peripheral nociception and central antinociception, conditioned aversion response to drugs, anxiety, and cognition. Because of the structural similarity between the nicotinic acetylcholine receptor and the 5HT3 receptor, we investigated the effects of clinically used neuromuscular blockers on the 5HT3 receptor function related with PONV.
METHODS
A cDNA clone encoding the full length murine 5HT3a receptor was subcloned into an oocyte expression vector and 50 ng of cRNA transcribed in vitro injected per oocyte. After 24 72 h incubation, oocytes were placed into a recording chamber continuously perfused with frog Ringer's solution and electrophysiological recordings were obtained by the two electrode voltage clamp technique. Serotonin with or without the various drugs were bath applied by a computer controlled solenoid valve. Peak currents induced by the drug applications were measured and dose responses were obtained.
RESULTS
The 5HT3 receptor expression in Xenopus oocyte was identified by the pharmacologic tools. Serotonin induced rapid inward currents, and thus was showed dose-dependent: KD = 2.5 micrometer, Hill coefficiency = 2.09. Inhibition by the neuromuscular blockers showed dose-dependence and their inhibitory potency on 5HT3 receptor (IC50) was in order of d-tubocurarine (0.046 micrometer) > vecuronium (16.32 micrometer) > gallamine (1,169 micrometer).
CONCLUSIONS
There was a different inhibitory effect of nicotinic cholinergic antagonists, clinically used neuromuscular blockers, on the 5HT3 receptor and a judicious selection of them might contribute to reducing the incidence of PONV clinically.

Keyword

Animal, Xenopus laevis oocyte; Neuromuscular relaxant, d-tubocurarine, gallamine, vecuronium; Receptor, cDNA, serotonin type 3 receptor

MeSH Terms

Anxiety
Baths
Cholinergic Antagonists
Clone Cells
Cognition
DNA, Complementary
Electrodes
Gallamine Triethiodide
Incidence
Nausea
Neuromuscular Blockade*
Neuromuscular Blocking Agents*
Nociception
Oocytes*
Peripheral Nervous System
Postoperative Nausea and Vomiting
Receptors, Nicotinic
RNA, Complementary
Serotonin*
Tubocurarine
Vecuronium Bromide
Vomiting
Xenopus*
Cholinergic Antagonists
DNA, Complementary
Gallamine Triethiodide
Neuromuscular Blocking Agents
RNA, Complementary
Receptors, Nicotinic
Serotonin
Tubocurarine
Vecuronium Bromide