Phospholipase D Activation by Endogenous 5-Hydroxytryptamine 2C Receptors Is Mediated by Gα13 and Pertussis Toxin-Insensitive Gβγ 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 α and free βγ subunits from G 13 heterotrimers are responsible for phospholipase D activation.