A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination.
We have previously shown that second-messenger-dependent kinases (cAMP-dependent kinase, protein kinase C) in the olfactory system are essential in terminating second-messenger signaling in response to odorants. We now document that subtype 2 of the beta-adrenergic receptor kinase (beta ARK) is also involved in this process. By using subtype-specific antibodies to beta ARK-1 and beta ARK-2, we show that beta ARK-2 is preferentially expressed in the olfactory epithelium in contrast to findings in most other tissues. Heparin, an inhibitor of beta ARK, as well as anti-beta ARK-2 antibodies, (i) completely prevents the rapid decline of second-messenger signals (desensitization) that follows odorant stimulation and (ii) strongly inhibits odorant-induced phosphorylation of olfactory ciliary proteins. In contrast, beta ARK-1 antibodies are without effect. Inhibitors of protein kinase A and protein kinase C also block odorant-induced desensitization and phosphorylation. These data suggest that a sequential interplay of second-messenger-dependent and receptor-specific kinases is functionally involved in olfactory desensitization.
University Stuttgart-Hohenheim, Institute of Zoophysiology, Stuttgart Federal Republic of Germany.
S
S
Schleicher
I
I
Boekhoff
J
J
Arriza
R J
RJ
Lefkowitz
H
H
Breer
D000818:Animals; D000906:Antibodies; D002540:Cerebral Cortex / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology*; D002923:Cilia / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases; D004848:Epithelium / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D007700:Kinetics; D009812:Odorants; D009833:Olfactory Pathways / Q000502:physiology*; D009928:Organ Specificity; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015398:Signal Transduction; D012903:Smell / Q000502:physiology*; D013997:Time Factors; D051552:beta-Adrenergic Receptor Kinases
D000906:Antibodies; D007106:Immune Sera; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D006493:Heparin; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases