Distinct thermodynamic parameters of serotonin 5-HT3 agonists and antagonists to displace [3H] granisetron binding

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Abstract

Specific binding of [3H]granisetron was examined to serotonin 5-HT3 receptors in synaptosomal membranes of rat cerebral cortex between 1 and 37°C. Displacing potencies were determined for 5-HT3 antagonists (granisetron, ondansetron, tropisetron, and d-tubocurarine) and agonists (5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, phenylbiguanide, m-chlorophenylbiguanide, and SR 57227A). Displacing potencies of the agonists decreased with decreasing temperature. In contrast, displacing potencies of all antagonists increased with decreasing temperature, whereas those of tropisetron and d-tubocurarine passed a maximum. Scatchard analysis of [3H] granisetron binding resulted in KD values lower than the IC50 values of granisetron and a decreasing number of binding sites at higher temperatures. It can be reconciled with temperature-dependent agonist and antagonist states of 5-HT3 receptors. A semiquantitative thermodynamic analysis was based on displacing potencies. The distinct patterns for the signs of entropy, enthalpy, and heat capacity changes on binding can be reconciled with ionic interactions for agonists and hydrophobic interactions for antagonists. The distinctive differences in these thermodynamic parameters exceed those for GABAA and glycine receptor-ionophore complexes.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalJournal of neurochemistry
Volume67
Issue number1
DOIs
Publication statusPublished - Jul 1996

Keywords

  • Distinction of serotonin 5-HT3 agonists and antagonists
  • Granisetron binding
  • Neurotransmitter receptor-ionophore complexes
  • Serotonin 5-HT receptors
  • Thermodynamics of binding

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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