The Role of Rho and Rho-Dependent Kinase in Serotonin-Induced Contraction Observed in Bovine Middle Cerebral Artery
YASUMASA NISHIKAWA,1,2 MAMORU DOI,1 TAKAHIRO KOJI,1 MIKIO WATANABE,1 SHINGO KIMURA, SATOSHI KAWASAKI, AKIRA OGAWA1 and KAZUHIKO SASAKI
Department of Physiology, and 1Department of Neurosurgery, School of Medicine, Iwate Medical University, Morioka 020-8505, and 2Department of Rehabilitation, Morioka National Hospital, Morioka 020-0133
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 Ca2+-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.
keywords —— smooth muscle contraction; Rho-kinase; Rho; serotonin
© 2003 Tohoku University Medical Press
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Tohoku J. Exp. Med., 2003, 201, 239-249
Address for reprints: Yasumasa Nishikawa, M.D., Ph.D., Department of Physiology, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan.
e-mail: ynishikawa@mail.goo.ne.jp, ksasaki@iwate-med.ac.jp
Preliminary results from this study have been presented at the Annual Meeting of the Physiological Society of Japan, the Pathophysiological Society of Japan, and the Annual Meeting of Neurosurgery.