Influence of anesthetics on endogenous and recombinantly expressed G protein-coupled receptors in the Xenopus oocyte

Abstract

1. The oocyte of the African clawed toad ( Xenopus laevis) offers a reliable, sensitive and disease resistant system to investigate recombinantly and endogenously expressed Ca 2+ signaling G protein-coupled receptors and their intracellular signaling pathways. 2. To study receptor induced Ca 2+ release, two-electrode voltage clamping can quantify a Ca 2+-activated transmembrane Cl − current. Intracellular steps of the signaling pathway can be inhibited by injections of EDTA or heparin into the oocyte. Components of the intracellular pathway can be activated directly by GTP γS or IP 3 injection. 3. We have investigated the effects of volatile, local and i.v. anesthetics on the signaling properties of the endogenous lysophosphatidate receptor and on mammalian receptors expressed recombinantly by intracellular injection of the encoding mRNA or cDNA. A number of receptors are sensitive to these anesthetics. Anesthetics interact with muscarinic, thromboxane A 2 and lysophosphatidate signaling. 4. Investigations of the intracellular pathways revealed that the receptor or the receptor-G protein coupling is affected primarily and that mechanisms further downstream are not influenced by the various types of anesthetics.