Abstract
The current study was designed to characterize the role of Rho and Rho-dependent kinase (Rho-kinase) in isometric contractile responses induced by serotonin (5-HT) and a solution containing 40 mM K(+) (high K(+)) in ring preparations of the middle cerebral artery of bovine. Application of W-7, a Ca(2+)-calmodulin inhibitor, reversibly and equally attenuated the amplitudes of contractions produced by both 5-HT and high K(+). Similar effects were observed with ML-7, an inhibitor of myosin light chain kinase. Surprisingly, the protein kinase C inhibitors, calphostin C and Ro-31-8220, had no effect on the 5-HT-induced contraction. Incubation of preparations with Clostridium difficile toxin A and B or with Clostridium botulinum C3 exoenzyme for 48 hours attenuated the 5-HT-induced response but not the high K(+)-induced response. Application of the Rho-kinase inhibitor, Y-27632, resulted in marked inhibition of the 5-HT-induced response but had negligible effect on the high K(+)-induced response. These results suggest that the activation of Rho and Rho-kinase may be involved in the generation of the contraction produced by 5-HT in the bovine middle cerebral artery, while protein kinase C plays, if any, an insignificant role on the contraction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / metabolism
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Amides / pharmacology
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Animals
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Azepines / pharmacology
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Bacterial Proteins*
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Bacterial Toxins / pharmacology
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Botulinum Toxins / metabolism
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Brain
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Cattle
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Cerebral Arteries / drug effects*
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Cerebral Arteries / metabolism
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Cytotoxins / pharmacology
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Dose-Response Relationship, Drug
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Enterotoxins / pharmacology
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Enzyme Inhibitors / pharmacology
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Indoles / pharmacology
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Intracellular Signaling Peptides and Proteins
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Middle Cerebral Artery / drug effects*
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Middle Cerebral Artery / metabolism
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Myosin-Light-Chain Kinase / antagonists & inhibitors
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Naphthalenes / antagonists & inhibitors
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Naphthalenes / pharmacology
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Potassium / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Serine-Threonine Kinases / physiology*
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Pyridines / pharmacology
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Serotonin / pharmacology*
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Sulfonamides / pharmacology
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Time Factors
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rho GTP-Binding Proteins / physiology*
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rho-Associated Kinases
Substances
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Amides
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Azepines
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Bacterial Proteins
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Bacterial Toxins
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Cytotoxins
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Enterotoxins
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Enzyme Inhibitors
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Indoles
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Intracellular Signaling Peptides and Proteins
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Naphthalenes
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Pyridines
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Sulfonamides
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tcdA protein, Clostridium difficile
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toxB protein, Clostridium difficile
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ML 7
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Y 27632
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Serotonin
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W 7
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ADP Ribose Transferases
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exoenzyme C3, Clostridium botulinum
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinases
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Myosin-Light-Chain Kinase
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Botulinum Toxins
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rho GTP-Binding Proteins
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calphostin C
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Potassium
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Ro 31-8220