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- Title
A complex signaling cascade links the serotonin<sub>2A</sub> receptor to phospholipase A<sub>2</sub> activation: the involvement of MAP kinases.
- Authors
Kurrasch-Orbaugh, Deborah M.; Parrish, Jason C.; Watts, Val J.; Nichols, David E.
- Abstract
Abstract Previous studies in our laboratory have shown that in NIH3T3–5HT2A cells, 5-HT-induced AA release is PLA2 -coupled and independent of 5-HT2A receptor-mediated PLC activation. Although 5-HT2A receptor-mediated PLC activation is known to be Gαq -coupled, much less is understood about 5-HT2A receptor-mediated PLA2 activation. Therefore, the studies presented here were aimed at elucidating the signal transduction pathway linking stimulation of the 5-HT2A receptor to PLA2 activation. By employing various selective inhibitors, toxins, and antagonistic peptide constructs, we propose that the 5-HT2A receptor can couple to PLA2 activation through two parallel signaling cascades. Initial experiments were designed to examine the role of pertussis toxin-sensitive G proteins, namely Gαi/o , as well as pertussis toxin-insensitive G proteins, namely Gα12/13 , in 5-HT-induced AA release. Furthermore, inactivation of both Gβγ heterodimers and Rho proteins resulted in decreased agonist-induced AA release, without having any effect on PLC-IP accumulation. We also demonstrated 5-HT2A receptor-mediated phosphorylation of ERK1,2 and p38. Moreover, pretreatment with selective ERK1,2 and p38 inhibitors resulted in decreased 5-HT-induced AA release. Taken together, these results suggest that the 5-HT2A receptor expressed in NIH3T3 cells can couple to PLA2 activation though a complex signaling mechanism involving both Gαi/o -associated Gβγ-mediated ERK1,2 activation and Gα12/13 -coupled, Rho-mediated p38 activation.
- Subjects
CELLULAR signal transduction; G proteins; PHOSPHORYLATION
- Publication
Journal of Neurochemistry, 2003, Vol 86, Issue 4, p980
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01921.x