title: The role of rho and rho-dependent kinase in serotonin-induced contraction observed in bovine middle cerebral artery.
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.
authors.affiliation: Department of Physiology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan. ynishikawa@mail.goo.ne.jp
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Doi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Koji
authors.forename: Mikio
authors.initials: M
authors.lastname: Watanabe
authors.forename: Shingo
authors.initials: S
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Ogawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D001905:Botulinum Toxins / Q000378:metabolism; D001921:Brain; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D001381:Azepines; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D004768:Enterotoxins; D004791:Enzyme Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D009281:Naphthalenes; D011725:Pyridines; D013449:Sulfonamides; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; C070571:ML 7; C108830:Y 27632; D012701:Serotonin; C017967:W 7; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins; C058819:calphostin C; D011188:Potassium; C064758:Ro 31-8220