Abstract
We previously demonstrated that the mouse EP3beta receptor and its C-terminal tail-truncated receptor (abbreviated T-335) expressed in Chinese hamster ovary cells showed agonist-dependent and fully constitutive Gi activity in forskolin-stimulated cAMP accumulation, respectively. Here we examined the effect of the EP3beta receptor or T-335 receptor on adenylyl cyclase activity stimulated by the Gs-coupled EP2 subtype receptor in COS-7 cells. As a result, sulprostone, a selective EP3 agonist, dose dependently augmented butaprost-stimulated adenylyl cyclase activity in EP3beta receptor- or T-335 receptor-expressing COS-7 cells. However, such adenylyl cyclase augmentation was not attenuated by either pertussis toxin treatment or expression of the PH domain of rat betaARK1, which serves as a scavenger of Gbetagamma subunits, but was partially attenuated by treatment with either 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester, an intracellular Ca(2+) chelator, or W-7, a calmodulin inhibitor. These findings suggest that the C-terminal tail of the EP3beta receptor is not essentially involved in activation of EP2 receptor-stimulated adenylyl cyclase in a Ca(2+)/calmodulin-dependent but Gbetagamma subunit-independent manner.
(c)2002 Elsevier Science.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Diphosphate / metabolism
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Adenylate Cyclase Toxin
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Adenylyl Cyclases / metabolism*
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Alprostadil / analogs & derivatives*
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Alprostadil / pharmacology
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Animals
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COS Cells
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Calcium / metabolism
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Calmodulin / metabolism
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Cell Membrane / metabolism
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Chelating Agents / pharmacology
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Cloning, Molecular
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Cyclic AMP / metabolism
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DNA, Complementary / metabolism
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Dinoprostone / analogs & derivatives*
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Dinoprostone / pharmacology
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Dose-Response Relationship, Drug
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Egtazic Acid / analogs & derivatives*
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Egtazic Acid / pharmacology
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Enzyme Inhibitors / pharmacology
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
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Pertussis Toxin
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Prostaglandins / metabolism*
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Prostaglandins E, Synthetic / pharmacology
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Protein Structure, Tertiary
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Rats
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Receptors, Prostaglandin E / metabolism*
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Receptors, Prostaglandin E, EP3 Subtype
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Sulfonamides / pharmacology
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Virulence Factors, Bordetella / pharmacology
Substances
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Adenylate Cyclase Toxin
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Calmodulin
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Chelating Agents
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DNA, Complementary
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Enzyme Inhibitors
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Prostaglandins
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Prostaglandins E, Synthetic
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Ptger3 protein, mouse
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Ptger3 protein, rat
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP3 Subtype
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Sulfonamides
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Virulence Factors, Bordetella
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sulprostone
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Egtazic Acid
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Adenosine Diphosphate
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W 7
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Cyclic AMP
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Pertussis Toxin
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GTP-Binding Protein alpha Subunits, Gi-Go
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Adenylyl Cyclases
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Alprostadil
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butaprost
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Dinoprostone
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Calcium