To assign the GTP-binding protein (G-protein) subtype involved in the signal transduction from exogenous receptors to phospholipase C in the Xenopus oocyte translation system, antisense DNA complementary to rat G-protein alpha-subunit mRNA was designed and injected together with rat brain poly(A)+ RNA. Current response of mRNA-injected oocytes to acetylcholine (ACh) was suppressed dose-dependently by a co-injection of Gil alpha-antisense DNA, but response of the same oocytes to serotonin (5-HT) was not inhibited. In the oocytes co-injected with Go alpha-antisense DNA, the 5-HT response was more effectively suppressed than the ACh response. These results suggest that Go alpha but not Gil alpha intermediates brain 5-HT1C receptor function, and in contrast, muscarinic receptors derived from rat brain utilize Gil alpha rather than Go alpha to activate phospholipase C.