Inhibition of the constitutive activity of human 5‐HT1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY 100,635
- 3 February 1997
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 120 (5), 737-739
- https://doi.org/10.1038/sj.bjp.0701025
Abstract
At recombinant human 5-hydroxytryptamine (5-HT)5-HT1A receptors expressed in Chinese hamster ovary cells (CHO-5-HT1A), 5-carboxamidotryptamine (5-CT), acted as a full agonist (relative to 5-HT = 100%) for stimulation of receptor-mediated [35S]-GTP gamma S (guanylyl 5'-[gamma-thio]-tryphosphate) binding. In contrast, spiperone inhibited basal [35S]-GTP gamma S binding by 30.2% (IC50 = 55.5 nM) in CHO-5-HT1A membranes but not in control untransfected membranes. The antagonist, N-[2-[4-(2-methoxyphenyl) -1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclohexane-carboxamide (WAY 100,635), blocked both 5-CT-induced stimulation and spiperone-induced inhibition of [35S]-GTP gamma S binding without itself modifying [35S]-GTP gamma S binding. It is concluded that, in this heterologous expression system, 5-HT1A receptors display 'constitutive' activation of G-proteins and that spiperone displays inverse agonist activity whereas WAY 100,635 acts as a 'neutral' antagonist at this site.Keywords
This publication has 7 references indexed in Scilit:
- S 15535 and WAY 100,635 antagonise 5-HT-stimulated [35S]GTPγS binding at cloned human 5-HT1A receptorsEuropean Journal of Pharmacology, 1996
- Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonistBehavioural Brain Research, 1995
- Pharmacological Characterisation of [35S]-GTPγS Binding to Chinese Hamster Ovary Cell Membranes Stably Expressing Cloned Human 5-HT1DReceptor SubtypesJournal of Receptors and Signal Transduction, 1995
- Constitutively active 5-hydroxytryptamine2C receptors reveal novel inverse agonist activity of receptor ligands.Journal of Biological Chemistry, 1994
- Estimation of competitive antagonist affinity from functional inhibition curves using the Gaddum, Schild and Cheng‐Prusoíf equationsBritish Journal of Pharmacology, 1993
- Characterization of recombinant human serotonin 5HT1A receptors expressed in Chinese Hamster Ovary cells: [3H]spiperone discriminates between the G-protein-coupled and -uncoupled formsBiochemical Pharmacology, 1993
- High-level stable expression of recombinant 5-HT1A 5-hydroxytryptamine receptors in Chinese hamster ovary cellsBiochemical Journal, 1992