Calcium-sensitive particulate guanylyl cyclase as a modulator of cAMP in olfactory receptor neurons.
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.
Moon
C
C
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Jaberi
P
P
Otto-Bruc
A
A
Baehr
W
W
Palczewski
K
K
Ronnett
G V
GV
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D002923:Cilia / Q000201:enzymology*; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000502:physiology*; D051604:Guanylate Cyclase-Activating Proteins; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000502:physiology; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D010316:Particle Size; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D002135:Calcium-Binding Proteins; D051604:Guanylate Cyclase-Activating Proteins; D009419:Nerve Tissue Proteins; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D002118:Calcium