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]‐GTPγS (guanylyl 5′‐[γ‐thio]‐tryphosphate) binding. In contrast, spiperone inhibited basal [35S]‐GTPγS 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]‐GTPγS binding without itself modifying [35S]‐GTPγS 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.British Journal of Pharmacology (1997) 120, 737–739; doi:10.1038/sj.bjp.0701025Keywords
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