title: Identification and characterization of a new serotonergic recognition site with high affinity for 5-carboxamidotryptamine in mammalian brain.
abstract: We analyzed the existence of an additional serotonin (5-HT) receptor subtype, sensitive to 5-carboxamidotryptamine, in the mammalian brain. Radioligand binding studies with [3H]5-HT were carried out in rat, guinea pig, and human brain membranes, in the presence of unlabeled drugs to mask the binding to all known 5-HT receptors, with the exception of 5-HT1E sites. Under these conditions, unlabeled 5-carboxamidotryptamine still showed a biphasic competition curve with a nanomolar affinity component. Saturation studies with 5-[3H]carboxamidotryptamine were carried out in the presence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, mesulergine, and ergotamine, to mask the binding to all receptors known to be labeled by 5-carboxamidotryptamine. These studies showed the existence in cortex and hippocampus from guinea pig and human brain of a remaining binding site with high affinity (pK(D) = 7.8-8.1) and a unique pharmacological profile. 5-HT and 5-carboxamidotryptamine showed nanomolar affinity, whereas 5-methoxytryptamine recognized this binding site with intermediate affinity. Other drugs exhibited low or very low potency in inhibiting this binding. The addition of 5'-guanylylimidodiphosphate significantly reduced the number of binding sites labeled by 5-[3H]carboxamidotryptamine, in the presence of the masking drugs described above, indicating the interaction with a GTP-binding protein. Preliminary autoradiographic studies in human brain appear to indicate that this 5-HT binding site is present in areas such as the globus pallidus, neocortex, and hippocampus, among others.
authors.affiliation: Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Castro
authors.forename: T
authors.initials: T
authors.lastname: Romón
authors.forename: M J
authors.initials: MJ
authors.lastname: Castillo
authors.forename: E
authors.initials: E
authors.lastname: del Olmo
authors.forename: A
authors.initials: A
authors.lastname: Pazos
authors.forename: C
authors.initials: C
authors.lastname: del Arco
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D004878:Ergotamine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D008297:Male; D008322:Mammals; D008875:Middle Aged; D009928:Organ Specificity; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium
chemical_list: D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; D004878:Ergotamine; C031649:mesulergine