Identification of a 5-HT1 recognition site in human brain membranes different from 5-HT1A, 5-HT1B and 5-HT1C sites.
In human caudate and cortex membranes, [3H]serotonin ([3H]5-HT) labels 5-HT1A and 5-HT1C recognition sites which show nanomolar affinity for 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and mesulergine respectively, whereas no 5-HT1B binding could be identified. However, the majority of the sites labelled by [3H]5-HT (greater than or equal to 60% in cortex, 90% in caudate) are different from 5-HT1A, 5-HT1B and 5-HT1C sites. Competition experiments were performed in human caudate membranes incubated with [3H]5-HT in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine. Under those conditions, [3H]5-HT labelled an apparently homogeneous population of 5-HT1-like sites which display nanomolar affinity for tryptamines (5-carboxamido-tryptamine, (5-CT) greater than 5-HT greater than or equal to 5-methoxytryptamine (5-MeOT) greater than tryptamine) and some ergolines (metergoline greater than methysergide). In contrast, these sites showed low affinity for drugs with high affinity and/or selectivity for 5-HT1A (8-OH-DPAT, buspirone), 5-HT1B (21-009, RU 24969), 5-HT1C (mesulergine, mianserin) and 5-HT2 sites (ketanserin, cinanserin). The pharmacological profile of these sites is different from that of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 and 5-HT3 sites but is consistent with the pharmacology of a 5-HT1-like receptor. It is very similar to that of the 5-HT1D site recently described in bovine brain by Heuring and Peroutka.
Hoyer
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Sandoz Ltd., Basel, Switzerland.
Waeber
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C
Pazos
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Probst
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Palacios
J M
JM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001667:Binding, Competitive; D001923:Brain Chemistry; D002421:Caudate Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004873:Ergolines / Q000378:metabolism; D006801:Humans; D011985:Receptors, Serotonin / Q000032:analysis*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D004873:Ergolines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C031649:mesulergine