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J Biol Chem, Vol. 273, Issue 28, 17498-17503, July 10, 1998
§,
From the The study of signaling cascades and of functional
interactions between 5-hydroxytryptamine (5-HT) receptor pathways with
heterogenous brain cell populations remains an arduous task. We took
advantage of a serotonergic cell line to elucidate cross-talks between
5-HT receptors and to demonstrate the involvement of two 5-HT2 receptor subtypes in the regulation of 5-HT1B/1D function. The inducible 1C11
cell line has the unique property of acquiring within 4 days a complete
serotonergic phenotype (1C11* cells), including three 5-HT receptors.
5-HT1B/1D and 5-HT2B receptors are expressed since day 2 of the
serotonergic differentiation while 5-HT2A receptors are induced at day
4. We first established that 5-HT2B receptors are coupled with the
phospholipase A2 (PLA2)-mediated release of arachidonic acid (AA) and
that the activation of 5-HT2B receptors in 1C11*d2 cells inhibits the
5-HT1B/1D receptor function via a cyclooxygenase-dependent
AA metabolite. At day 4, this 5-HT2B-mediated inhibition of the
5-HT1B/1D function can be blocked upon concomitant 5-HT2A activation
although a 5-HT2A/PLA2 positive coupling was evidenced. This suggests
the existence in 1C11*d4 cells of pathway(s) for 5-HT2A receptors,
distinct from PLC and PLA2. Finally, this study reveals the
antagonistic roles of 5-HT2A and 5-HT2B receptors in regulating the
function of 5-HT1B/1D, a receptor involved in neuropsychiatric
disorders and migraine pathogenesis.
Différenciation Cellulaire, CNRS URA
1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France, the ¶ Pharma Research Department, Hoffmann-La-Roche A.G.,
4002 Basel, Switzerland, and the § CR C. Bernard, Pathologie
Expérimentale et Communications Cellulaires, IFR 6, Service de
Biochimie, Hôpital Lariboisière, 75010 Paris, France and
Laboratoire de Biologie Cellulaire, Faculté de Pharmacie,
Université Paris V, 75006 Paris, France
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