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

Abstract：

:Specific binding of [3H]granisetron was examined to serotonin 5-HT3 receptors in synaptosomal membranes of rat cerebral cortex between 1 and 37 degrees 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.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Maksay G

doi

10.1046/j.1471-4159.1996.67010407.x

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

407-12

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

67

pub_type

杂志文章

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