The G-protein-coupled receptor kinases βARK1 and βARK2 are widely distributed at synapses in rat brain

The β-adrenergic receptor kinase (βARK) phosphorylates the agonist- occupied β-adrenergic receptor to promote rapid receptor uncoupling from G(s), thereby attenuating adenylyl cyclase activity. βARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding βARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed βARK1 and βARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The βARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, βARK1 and βARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The βARK isozymes have a regional and subcellular distribution consistent with a general role in the desensitization of synaptic receptors.