Pharmacological Dissection of G Protein-Mediated Second Messenger Cascades in Neurons

Despite the advent of transgenic gene manipulation in vivo and in vitro and the rapid rise of RNA interference, in order to target protein function by ablation or suppression of specific gene products, pharmacological manipulation of G protein-coupled signalling pathways remains a highly useful tool for understanding receptor coupling to effector mechanisms in neurons. The key to drawing valid conclusions from pharmacological manipulations is a solid knowledge of the signalling pathway molecules and on- and off-target effects of the pharmacological tools to be used. This chapter outlines the actions, application and pitfalls of pharmacological ligands commonly used to dissect the major second messenger signalling cascades activated by G proteins in neurons. Despite the limitations of many currently used pharmacological tools, careful and judicious use of these tools allows the exploration and definition of these pathways at all levels.