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The Journal of Neuroscience, May 1, 1998, 18(9):3195-3205
Calcium-Sensitive Particulate Guanylyl Cyclase as a Modulator of
cAMP in Olfactory Receptor Neurons
Cheil
Moon1,
Parham
Jaberi1,
Annie
Otto-Bruc3,
Wolfgang
Baehr5,
Krzysztof
Palczewski3, 4, and
Gabriele V.
Ronnett1, 2
Departments of 1 Neuroscience and
2 Neurology, Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205, Departments of 3 Ophthalmology
and 4 Pharmacology, School of Medicine, University of
Washington, Seattle, Washington 98185, and 5 Moran Eye
Center, University of Utah Health Science Center, Salt Lake City, Utah
84132
The second messengers cAMP and inositol-1,4,5-triphosphate have
been implicated in olfaction in various species. The odorant-induced cGMP response was investigated using cilia preparations and olfactory primary cultures. Odorants cause a delayed and sustained elevation of
cGMP. A component of this cGMP response is attributable to the
activation of one of two kinetically distinct cilial receptor guanylyl
cyclases by calcium and a guanylyl cyclase-activating protein (GCAP).
cGMP thus formed serves to augment the cAMP signal in a cGMP-dependent
protein kinase (PKG) manner by direct activation of adenylate cyclase.
cAMP, in turn, activates cAMP-dependent protein kinase (PKA) to
negatively regulate guanylyl cyclase, limiting the cGMP signal. These
data demonstrate the existence of a regulatory loop in which cGMP can
augment a cAMP signal, and in turn cAMP negatively regulates cGMP
production via PKA. Thus, a small, localized, odorant-induced cAMP
response may be amplified to modulate downstream transduction enzymes
or transcriptional events.
Key words:
olfaction; signal transduction; guanylyl cyclase; olfactory receptor neuron; cilia; protein kinase
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893195-11$05.00/0
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