Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism.
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.
Tournois
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C
Différenciation Cellulaire, CNRS URA 1960, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Mutel
V
V
Manivet
P
P
Launay
J M
JM
Kellermann
O
O
D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction
D011985:Receptors, Serotonin; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2