Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development.
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.
Grimaldi
B
B
Unité de Pharmacologie-Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Bonnin
A
A
Fillion
M P
MP
Ruat
M
M
Traiffort
E
E
Fillion
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000187:drug effects; D018490:Serotonin Agents / Q000494:pharmacology; D014162:Transfection
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D018490:Serotonin Agents; C097216:serotonin 6 receptor; D000262:Adenylyl Cyclases