BETA-ADRENERGIC-RECEPTOR KINASE-2 AND BETA-ARRESTIN-2 AS MEDIATORS OF ODORANT-INDUCED DESENSITIZATION

Beta-adrenergic receptor kinase (betaARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors. The isoforms betaARK-2 and beta-arrestin-2 are highly enriched in and localized to the dendritic knobs and cilia of the olfactory receptor neurons where the initial events of olfactory signal transduction occur. Odorants induce a rapid and transient elevation of adenosine 3',5'-monophosphate (cAMP), which activates a nonspecific cation channel and produces membrane depolarization. Preincubation of rat olfactory cilia with antibodies raised against betaARK-2 and beta-arrestin-2 increased the odorant-induced elevation of cAMP and attenuated desensitization. These results suggest that betaARK-2 and beta-arrestin-2 mediate agonist-dependent desensitization in olfaction.