G PROTEIN-COUPLED RECEPTOR KINASE MEDIATES DESENSITIZATION OF NOREPINEPHRINE-INDUCED CA2+ CHANNEL INHIBITION

G protein-coupled receptors are essential signaling molecules at sites of synaptic transmission. Here, we explore the mechanisms responsible for the use-dependent termination of metabotropic receptor signaling in embryonic sensory neurons. We report that the inhibition of voltage -dependent Ca2+ channels mediated by alpha(2)-adrenergic receptors des ensitizes slowly with prolonged exposure to the transmitter and that t he desensitization is mediated by a G protein-coupled receptor kinase (GRK). Intracellular introduction of recombinant, purified kinases or synthetic blocking peptides into individual neurons demonstrates the s pecific involvement of a GRK3-like protein. These results suggest that GRK-mediated termination of receptor-G protein coupling is likely to regulate synaptic strength and, as such, may provide one effective mec hanism for depression of synaptic transmission.