G_oprotein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway

RECEPTORS stimulating phospholipase C do so through heterotrimeric GTP-binding proteins^1,2 to produce two second messengers, inositol 1,4,5-trisphosphate (InsP₃) and diacylgly-cerol¹. In spite of the detailed understanding of phospholipase C structure3 and phosphatidyl inositol signalling¹, the identity of the GTP-binding protein involved is so far unknown. To address this issue, we have used the Xenopus oocyte in which muscarinic receptors couple to phospholipase C through a pertussis toxin-sensitive GTP-binding protein². In this cell, InsP₃ mobilizes intracellular Ca²1 to evoke a Cl^-current. The magnitude of this Cl^- current is proportional to the amount of InsP₃ in the cell⁴, and therefore can be used as an assay for InsP₃ production. We report here that the activated a-subunit of the GTP-binding protein G0, when directly injected into oocytes, evokes a Cl^- current by mobilizing Ca²⁺ from intracellular InsP₃-sensitive stores. We also show that holo-G_O, when injected into oocytes, can specifically enhance the muscarinic receptor-stimulated Cl current. These data indicate that G_O can serve as the signal transducer of the receptor-regulated phospholipase C inXenopus oocytes.