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Inhibition of the constitutive activity of human 5‐HT 1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY 100,635
Author(s) -
NewmanTancredi Adrian,
Conte Caroline,
Chaput Christine,
Spedding Michael,
Millan Mark J
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701025
Subject(s) - spiperone , inverse agonist , agonist , gtp' , receptor , antagonist , chinese hamster ovary cell , g protein , stimulation , chemistry , competitive antagonist , endocrinology , medicine , biology , biochemistry , enzyme
At recombinant human 5‐hydroxytryptamine (5‐HT)5‐HT 1A receptors expressed in Chinese hamster ovary cells (CHO‐5‐HT 1A ), 5‐carboxamidotryptamine (5‐CT), acted as a full agonist (relative to 5‐HT=100%) for stimulation of receptor‐mediated [ 35 S]‐GTPγS (guanylyl 5′‐[γ‐thio]‐tryphosphate) binding. In contrast, spiperone inhibited basal [ 35 S]‐GTPγS binding by 30.2% (IC 50 =55.5 n m ) in CHO‐5‐HT 1A 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 [ 35 S]‐GTPγS binding without itself modifying [ 35 S]‐GTPγS binding. It is concluded that, in this heterologous expression system, 5‐HT 1A 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.0701025