Abstract
The second messengers 3'-5'-cyclic-monophosphate (cAMP) and inositol 1,4,5-trisphosphate (InsP3) have been implicated in olfactory signal transduction in various species. The results of the present study provide evidence that the two olfactory second messenger pathways in rat olfactory neurons do not work independently but rather show a functional antagonism: whereas inhibition of phospholipase C (PLC) in isolated olfactory cilia by U-73122 led to an augmentation of odor-induced cAMP signaling, activation of the phosphoinositol pathway resulted in attenuation of odor-induced cAMP formation. Furthermore, this study indicates that elevated cAMP levels cause suppression of odor-induced InsP3 signaling, whereas inhibition of adenylate cyclase (AC) by cisN-(2-phenylcyclopentyl)azacylotridec-1-en-2-amine (MDL-12,330 A) results in potentiation of odor-induced InsP3 formation. Concerning the molecular mechanism involved in cross-interaction, the experimental data indicate that the observed antagonism of elevated cAMP is based on inhibition of PLC activation rather than on stimulation of InsP3 degradation. As blockage of the endogenous protein kinase A (PKA) prevented the inhibitory effect of cAMP, the suppression of odor-induced InsP3 signaling by cAMP may be mediated by a PKA-controlled reaction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclase Inhibitors
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Animals
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Cilia / drug effects
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Cilia / enzymology
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Colforsin / pharmacology
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Imines / pharmacology
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Inositol 1,4,5-Trisphosphate / antagonists & inhibitors
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Inositol 1,4,5-Trisphosphate / metabolism
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Intercellular Signaling Peptides and Proteins
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Olfactory Pathways / chemistry*
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Olfactory Pathways / drug effects
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Olfactory Pathways / physiology*
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Peptides / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Pyrrolidinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction
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Second Messenger Systems / drug effects
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Second Messenger Systems / physiology*
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Type C Phospholipases / antagonists & inhibitors
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Type C Phospholipases / metabolism
Substances
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Adenylyl Cyclase Inhibitors
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Enzyme Inhibitors
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Estrenes
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Imines
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Intercellular Signaling Peptides and Proteins
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Peptides
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Walsh peptide
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Colforsin
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RMI 12330A
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Inositol 1,4,5-Trisphosphate
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Type C Phospholipases