Allosteric modulation of 5-HT3 serotonin receptors

G. Maksay, Tímea Bíró, Gyula Bugovics

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

[3H]Granisetron binding to 5-HT3 type serotonin receptors was examined in homogenates of rat forebrain and NG 108-15 cells. We have applied an allosteric model to 5-HT3 receptor binding for the first time. Slope factors of displacement improved the modelling. Serotonin displaced [3H]granisetron binding with micromolar potency in forebrain and with nanomolar potency in NG 108-15 cells. Racemic and (+)verapamil, ifenprodil and GYKI-46903 were used as representative allosteric inhibitors of 5-HT3 receptors. They displaced [3H] granisetron binding with great negative cooperativity (α > 10) and exerted great negative cooperativity with serotonin binding (β > 10). Great negative cooperativity of these agents with serotonin and [ 3H]granisetron binding cannot be distinguished from dual competitive displacement. Trichloroethanol (data from literature) had no cooperativity with [3H]granisetron binding (α ∼ 1) and exhibit positive cooperativity with serotonin (β <1) in displacement. The allosteric model can lead to a more quantitative method in vitro to develop allosteric agents for 5-HT3 receptors.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalEuropean Journal of Pharmacology
Volume514
Issue number1
DOIs
Publication statusPublished - May 2 2005

Fingerprint

Granisetron
Receptors, Serotonin, 5-HT3
Serotonin
Prosencephalon
Serotonin Agents
Verapamil

Keywords

  • 5-HT serotonin receptor binding
  • Allosteric modulation
  • Ifenprodil
  • NG 108-15 cell
  • Slope of displacement
  • Verapamil

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Allosteric modulation of 5-HT3 serotonin receptors. / Maksay, G.; Bíró, Tímea; Bugovics, Gyula.

In: European Journal of Pharmacology, Vol. 514, No. 1, 02.05.2005, p. 17-24.

Research output: Contribution to journalArticle

Maksay, G. ; Bíró, Tímea ; Bugovics, Gyula. / Allosteric modulation of 5-HT3 serotonin receptors. In: European Journal of Pharmacology. 2005 ; Vol. 514, No. 1. pp. 17-24.
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