Abstract
In the present study, the inhibitory effect of the cGMP analog (Rp)-8-(para-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate ((Rp)-8-pCPT-cGMPS) on the cGMP-dependent protein kinase-mediated protein phosphorylation in intact human platelets was investigated. In vitro phosphorylation experiments with the substrate kemptide demonstrated an inhibition of the cGMP-dependent protein kinase by (Rp)-8-pCPT-cGMPS with a Ki of 0.5 microM. In intact human platelets, (Rp)-8-pCPT-cGMPS antagonized the activation of the cGMP-dependent protein kinase by 8-pCPT-cGMP without affecting cAMP-dependent protein kinase or cGMP-regulated phosphodiesterases. The data obtained suggest that (Rp)-8-pCPT-cGMPS may be a useful tool for studying the role of cGMP in vitro and in intact cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Platelets / drug effects
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Blood Platelets / enzymology
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Blotting, Western
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Cattle
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Chemical Phenomena
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Chemistry, Physical
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / antagonists & inhibitors
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Cyclic GMP / pharmacology
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Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
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Cyclic GMP-Dependent Protein Kinases / metabolism
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Enzyme Activation / drug effects
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Humans
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In Vitro Techniques
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Oligopeptides / metabolism
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Phosphorylation
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Platelet Aggregation Inhibitors / pharmacology
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Thionucleotides / antagonists & inhibitors
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Thionucleotides / pharmacology
Substances
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Oligopeptides
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Platelet Aggregation Inhibitors
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Thionucleotides
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8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
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kemptide
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Cyclic AMP-Dependent Protein Kinases
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Cyclic GMP-Dependent Protein Kinases
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Cyclic GMP