Xenopus oocytes that express mouse thyrotropin-releasing hormone receptors (TRH-Rs) after injection if RNA transcribed from TRH-R cDNA respond to THR by a depolarizing current. This response is transducer by activation of phosphoinositide-specific phospholipase C and utilizes an as yet unidentified endogenous guanine nucleotide-binding regulatory (G) protein(s). The α subunit of G 1 1 and G q have recently been shown to couple receptors to activation of phospholipase C. To determine whether there are functional differences between these proteins, we have co-expressed the TRH-R with either α 1 1 or α q , α 1 1 potentiated the response to TRH (by 61+/-16%), while α q inhibited the response (by 37+/-9%). The changes in amplitudes were accompanied by inverse changes in response latencies. These data show that α 1 1 and α q differentially modulate signal transduction in Xenopus oocytes.