FUNCTIONAL COUPLING OF THE 5-HT2C SEROTONIN RECEPTOR TO G-PROTEINS IN XENOPUS OOCYTES

The serotonin 2C (5-HT2C) receptor mediates its cellular effects by interacting with heterotrimeric guanine nucleotide binding proteins (G proteins). To characterize which G proteins are involved in functional coupling to the receptor, a mouse 5-HT2C receptor was expressed in Xenopus oocytes, and antisense oligonucleotides complementary to the mRNA sequence of the endogenous Xenopus G protein alpha subunits were used to inhibit G protein synthesis. Antisense oligonucleotide against the Xenopus G(o) alpha subunit inhibited the 5-HT2C receptor function, and coexpression of a rat G(o) alpha subunit reversed the inhibition by the anti-Xenopus G(o) oligonucleotide. Furthermore, antisense oligonucleotides against both the G(o) and G(il) alpha subunits inhibited the electrophysiologic response induced by stimulation of the 5-HT2C receptor. These data suggest that both G(o) and G(il) are involved in functional coupling of the 5-HT2C receptor to phospholipase C in Xenopus oocytes.