The phosphoinositide second-messenger system is one of the major mechanisms utilized by cells to transduce signals originating from extracellular stimuli, such as neurotransmitters, to intracellular responses (Fisher, 1995). A variety of cellular components can contribute to the phosphoinositide second-messenger system to transduce signals. However, most commonly the phosphoinositide signal transduction system is considered to consist of receptors with seven membrane-spanning domains containing intracellular regions that are coupled with members of the Gq family of heterotrimeric G-proteins (with α-, β-, and γ-subunits) which, in turn, regulate the activity of the P-subtype of phospholipase C (Bristol and Rhee, 1995), an enzyme that cleaves the phosphoinositides (Fig. 1). In these systems, appropriate agonists induce conformational shifts in receptors which lead to activation of the coupled G-proteins. G-protein activation involves release of previously bound GDP, which is replaced with GTP in activated G-proteins (Gilman, 1987). This event can be mimicked experimentally by exposing G-proteins to stable analogs of GTP, such as GTPγS, or to solutions containing NaF and aluminum. In the latter case it is thought that AlF₄-is formed and binds the GDP that is bound to the G-protein to mimic the γ-phosphate of GTP (Bigay et al., 1985), thereby bypassing receptors to directly activate G-proteins.