MUSCARINIC M(3) RECEPTOR COUPLING AND REGULATION

Current concepts regarding the regulation and coupling of muscarinic m (3) receptors to G-proteins and various effecters are discussed. The l ast few years have provided much evidence that although muscarinic m(1 ), m(3) and m(5) subtypes couple predominantly via pertussis toxin-ins ensitive G-proteins (Gq/11) to activate phosphoinositidase C (PIC), in teractions with other G-proteins (Gi, Go, Gs) can be readily observed in cells expressing recombinant muscarinic receptors even at relativel y low levels. The significance of this diversity and the potential for agonist ''trafficking'' could open up opportunities for novel approac hes to selective agonist action. Finally, mechanisms underlying the re gulation of muscarinic m(3) coupling through Gq/11 to PIC are discusse d. In particular, our recent studies on precursor lipid depletion, whe ther regulation is receptor or cell specific and the identification an d role of receptor kinases are briefly reviewed.