Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Naunyn-Schmiedeberg's Archives of Pharmacology Année : 1998

Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development

Résumé

We have determined the pharmacological characteristics of the rat 5-ht6 receptor stably expressed in CHO cells. Moreover, using RT-PCR experiments the in vivo expression of the gene encoding this receptor was studied in rat at various embryonic days (ED) starting from ED10 to birth (PN0) and at post-natal days (PN) up to PN36. The pharmacological analysis of the [3H]5-HT binding in stably transfected CHO cells expressing rat 5-ht6 receptors revealed the presence of a single class of high affinity saturable binding sites for 5-HT corresponding to an affinity constant: Kd=27.2+/-3.4 nM. This receptor also exhibited a high affinity for a number of typical and atypical antipsychotics, tricyclic antidepressant drugs and ergot alkaloïds. In stably transfected CHO cells, serotonin elicited a potent stimulation of adenylyl cyclase activity which was blocked by antipsychotic and antidepressant drugs. These results confirm the hypothesis that 5-ht6 receptors may correspond to an important target for atypical antipsychotics and reveal an original pharmacological profile for this receptor. The study of the ontogeny of the 5-ht6 mRNA in rat developing brain showed that 5-ht6 mRNA were first detectable with a high level on ED12, slighly decreased up to ED17 and then remained stable at high level until the adult age. The ontogenetic pattern of 5-ht6 mRNA expression appeared to correlate with the occurence of the first cell bodies of serotonergic neurons; the early expression of 5-ht6 mRNA and the fact that this receptor is positively coupled to the production of cAMP may suggest a role for 5-ht6 receptor in the early growth process involving the serotonergic system.

Dates et versions

hal-03533908 , version 1 (19-01-2022)

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Citer

B. Grimaldi, Alexandre Bonnin, Marie-Paule Fillion, Martial Ruat, Elisabeth Traiffort, et al.. Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development. Naunyn-Schmiedeberg's Archives of Pharmacology, 1998, 357 (4), pp.393-400. ⟨10.1007/pl00005184⟩. ⟨hal-03533908⟩
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