Phospholipase D activation by endogenous 5-hydroxytryptamine 2C receptors is mediated by Galpha13 and pertussis toxin-insensitive Gbetagamma subunits.

Phospholipase D activation was measured in primary cultures of rat choroid plexus epithelial cells, which endogenously express the 5-hydroxytryptamine (5-HT) 2C receptor, as well as a heterologous cell line expressing the cloned receptor. In both systems, serotonin stimulation of the 5-HT(2C) receptor activates phospholipase D in addition to phospholipase C, the traditional effector. Specific inhibitors and membrane permeable blocking peptides were used to determine which heterotrimeric G-proteins were involved. Results suggest that both alpha and free betagamma subunits from G(13) heterotrimers are responsible for phospholipase D activation.