Neuron. 1996 Mar;16(3):579-85.

G protein-coupled receptor kinase mediates desensitization of norepinephrine-induced Ca2+ channel inhibition.

Diverse-Pierluissi M, Inglese J, Stoffel RH, Lefkowitz RJ, Dunlap K.

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Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Abstract

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 alpha2-adrenergic receptors desensitizes slowly with prolonged exposure to the transmitter and that the 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 specific 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 mechanism for depression of synaptic transmission.

PMID:: 8785055; [PubMed - indexed for MEDLINE]

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