Inhibitory effect of glucocorticoids on human-cloned 5-hydroxytryptamine3A receptor expressed in Xenopus oocytes

• Published in: Anesthesiology (Philadelphia) 2004-09, Vol.101 (3), p.660-665
• Main Authors: SUZUKI, Takahiro, SUGIMOTO, Masahiro, KOYAMA, Hideki, MASHIMO, Takashi, UCHIDA, Ichiro
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cloning, Molecular; Dexamethasone - pharmacology; DNA, Complementary - biosynthesis; DNA, Complementary - genetics; Electrophysiology; Glucocorticoids - pharmacology; Humans; Medical sciences; Membrane Potentials - drug effects; Methylprednisolone - pharmacology; Oocytes - metabolism; Patch-Clamp Techniques; Receptors, Serotonin, 5-HT3 - genetics; Recombinant Proteins; Serotonin Antagonists; Xenopus
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200409000-00014

Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes. Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current. Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor. The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.