Serotonin 2C receptor (5-HT2CR) mRNA editing-induced down-regulation of 5-HT2CR function in Xenopus oocytes: the significance of site C editing

Serotonin 2c receptor (5-ht2cr) mrna receives editing at 5 nucleotide positions (sites a-e) located in the sequence encoding the second intracellular loop of 5-ht2cr. 5-ht2cr mrna without editing and with editing at sites ab,abd,abc,abcd,and c are translated to 6 isoforms of 5-ht2cr: ini(non-edited),vni(ab),vnv(abd),vsi(abc),vsv(abcd),and isi(c),respectively. in this study,we investigated electrophysiologically the ability of these isoforms to couple with the g protein / phospholipase c (plc) system using xenopus oocytes injected with edited 5-ht2cr rnas and muscarinic m 1 receptor (m1r) rna. the efficacy with which 5-ht stimulated each isoform was calculated by comparing 5-ht-induced current with 100 μ m acetylcholine-induced m1r current. stimulation with 5-ht of ini(non-edited),vni(ab),vnv(abd),vsi(abc),vsv(abcd),and isi(c) expressed in xenopus oocytes showed concentration-dependent responses with ec 50 values of 8.6,17.2,76,5,22.0,91.2,and 20.3 nm,respectively. no significant difference in the ability of 5-ht to induce currents among the oocytes expressing these isoforms was detected,but in the oocytes expressing vsi(abc) or vsv(abcd),5-ht had a significantly reduced ability to induce currents. these results suggest that editing at site c together with sites a and b and/or d markedly reduces 5-ht2cr function by generating isoforms with reduced ability to activate plc. © 2010 the japanese pharmacological society.