THE SUBCELLULAR AND CELLULAR-DISTRIBUTION OF G-PROTEIN-COUPLED-RECEPTOR-KINASE-2 IN RAT-BRAIN

G protein-coupled receptor kinase 2 has been found to phosphorylate an d thus regulate the activity of several G protein-coupled receptors im plicated in neuronal signalling pathways. Although this kinase was ini tially described as a soluble protein, our laboratory has recently fou nd that a significant amount of G protein-coupled receptor kinase 2 is associated with microsomal membranes in liver and different types of cultured cells. In the present report we show that high G protein-coup led receptor kinase 2 specific activity and protein levels are present in microsomal fractions of rat brain homogenates. On the other hand, immunochemical detection using a new antibody raised against the N-ter minus of the kinase revealed a specific and widely distributed stainin g in different areas of the central nervous system, and the associatio n of G protein-coupled receptor kinase 2 with intracellular structures in nervous cells. Our results further suggest that this receptor kina se may be involved in the modulation of G protein-coupled receptor-med iated neurotransmission and that association with microsomal membranes may play a role in G protein-coupled receptor kinase 2 functions in t he brain. (C) 1998 IBRO. Published by Elsevier Science Ltd.