Vol. 96, Issue 25, 14605-14610, December 7, 1999
Neurobiology
Odorants induce the phosphorylation of the cAMP response element
binding protein in olfactory receptor neurons
Cheil
Moon*,
Young-Kwan
Sung*,
Radhika
Reddy*, and
Gabriele V.
Ronnett*,
,
Departments of * Neuroscience and Neurology, The Johns
Hopkins University, Baltimore, MD 21205
Edited by Solomon H. Snyder, Johns Hopkins University School of
Medicine, Baltimore, MD, and approved October 11, 1999 (received for review June 16, 1999)
Although odorants are known to activate olfactory receptor neurons
through cAMP, the long-term effects of odorant detection are not known.
Our recent findings indicate that there is also a delayed and sustained
cAMP response, with kinetics sufficient to mediate long-term cellular
responses. This cAMP response is mediated by cGMP through activation of
adenylyl cyclase by protein kinase G (PKG). Therefore, we investigated
the ability of odorants to regulate gene expression in rat olfactory
epithelium. The cAMP-responsive binding protein (CREB) is a
well-characterized transcription factor regulated by cAMP. We examined
CREB activity in rat olfactory epithelium and olfactory receptor
neurons (ORNs) after stimulation with odorants. Odorants increased
levels of phosphorylated CREB in olfactory epithelium in
vivo, and this increase was localized to ORNs in
vitro. Incubation with 8-bromo-cGMP or sodium nitroprusside, a
guanylyl cyclase activator, also increased phosphorylated CREB. In vitro, cAMP-dependent protein kinase phosphorylated
CREB. In contrast, PKG failed to phosphorylate CREB directly in
vitro. Our results demonstrate that the delayed odorant-induced
cAMP signal activates CREB, which in turn may modulate gene expression in ORNs. In addition, cGMP indirectly affects CREB activation. This
effect of cGMP on CREB activity through cAMP provides another mechanism
for the modulation of CREB.
To whom reprint requests should be addressed.
E-mail: gabriele_ronnett{at}qmail.bs.jhu.edu.
Copyright © 1999 by The National Academy of Sciences 0027-8424/99/9614605-6$2.00/0
