Muscarinic M3 receptor coupling and regulation

Current concepts regarding the regulation and coupling of muscarinic m3 receptors to G-proteins and various effectors are discussed. The last few years have provided much evidence that although muscarinic m1, m3 and m5 subtypes couple predominantly via pertussis toxin-insensitive G-proteins (Gq/11) to activate phosphoinositidase C (PIC), interactions with other G-proteins (Gi, Go, Gs) can be readily observed in cells expressing recombinant muscarinic receptors even at relatively low levels. The significance of this diversity and the potential for agonist "trafficking" could open up opportunities for novel approaches to selective agonist action. Finally, mechanisms underlying the regulation of muscarinic m3 coupling through Gq/11 to PIC are discussed. In particular, our recent studies on precursor lipid depletion, whether regulation is receptor or cell specific and the identification and role of receptor kinases are briefly reviewed.