Schleicher S, Boekhoff I, Arriza J, Lefkowitz R J, Breer H
University Stuttgart-Hohenheim, Institute of Zoophysiology, Stuttgart Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1420-4. doi: 10.1073/pnas.90.4.1420.
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.
我们之前已经表明，嗅觉系统中依赖第二信使的激酶（环磷酸腺苷依赖性激酶、蛋白激酶C）在终止对气味剂的第二信使信号传导中至关重要。我们现在证明，β-肾上腺素能受体激酶2亚型（βARK）也参与这一过程。通过使用针对βARK-1和βARK-2的亚型特异性抗体，我们发现与大多数其他组织的情况不同，βARK-2在嗅觉上皮中优先表达。βARK的抑制剂肝素以及抗βARK-2抗体，（i）完全阻止了气味剂刺激后第二信使信号的快速下降（脱敏），并且（ii）强烈抑制气味剂诱导的嗅觉纤毛蛋白磷酸化。相比之下，βARK-1抗体则没有作用。蛋白激酶A和蛋白激酶C的抑制剂也能阻断气味剂诱导的脱敏和磷酸化。这些数据表明，依赖第二信使的激酶和受体特异性激酶的顺序相互作用在嗅觉脱敏中发挥着功能作用。
