TY - JOUR
T1 - Multiple activation mechanisms of serotonin-mediated contraction in the carotid arteries obtained from spontaneously hypertensive rats
AU - Watanabe, Shun
AU - Matsumoto, Takayuki
AU - Ando, Makoto
AU - Adachi, Tsuyuki
AU - Kobayashi, Shota
AU - Iguchi, Maika
AU - Takeuchi, Miki
AU - Taguchi, Kumiko
AU - Kobayashi, Tsuneo
N1 - Funding Information:
We would like to thank M. Nagata, M. Takahashi, A. Suwa, J. Nomoto, S. Hotozuka, M. Majima, and H. Sashikubi for the excellent technical assistance. This work was supported in part by JSPS KAKENHI Grant Numbers 26460107 (T.M.), 15K21419 (K.T.), and 15K07975 (T.K.). The authors would like to thank Enago ( www.enago.jp ) for the English language review.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Serotonin (5-hydroxytryptamine, 5-HT) is an important endogenous substance that regulates the vascular tone, and the abnormal signaling of 5-HT has been observed in the arteries under several pathophysiological conditions such as diabetes and hypertension. However, signaling pathways of 5-HT-mediated vasocontraction in hypertension remain unclear. Therefore, we tested the hypothesis that 5-HT-mediated contraction and contributions of various kinases such as mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K), Rho kinase (ROCK), and 3-phosphoinositide-dependent kinase 1 (PDK1) to the contraction would be altered in the carotid arteries obtained from spontaneously hypertensive rats (SHR) compared to control Wistar Kyoto (WKY) rats. In the carotid arteries from SHR (vs. those from WKY), (1) the 5-HT-mediated contraction was increased, whereas the norepinephrine-mediated contraction was not; (2) 5-HT-mediated contractions were partly inhibited by each kinase (extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase (JNK), PI3K, ROCK, and PDK1) inhibitor; and (3) 5-HT-stimulated phosphorylation of ERK1/2, p38 MAPK, JNK, myosin phosphatase target subunit 1 (MYPT1), and PDK1 was increased. The expression of ROCK2 but not ROCK1 was increased in the carotid arteries from SHR compared to WKY. The expression of 5-HT2A receptor, a major receptor of 5-HT-mediated contraction in rat carotid artery, was similar in carotid arteries between the two groups. These results suggest that 5-HT-mediated contraction was utilized multiple signaling pathways such as ERK1/2, p38 MAPK, JNK, PI3K, ROCK, and PDK1. Although 5-HT-mediated contraction was increased in the carotid arteries obtained from SHR, further studies are necessary to clarify how each kinase may integrate in the vascular smooth muscles under hypertension.
AB - Serotonin (5-hydroxytryptamine, 5-HT) is an important endogenous substance that regulates the vascular tone, and the abnormal signaling of 5-HT has been observed in the arteries under several pathophysiological conditions such as diabetes and hypertension. However, signaling pathways of 5-HT-mediated vasocontraction in hypertension remain unclear. Therefore, we tested the hypothesis that 5-HT-mediated contraction and contributions of various kinases such as mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K), Rho kinase (ROCK), and 3-phosphoinositide-dependent kinase 1 (PDK1) to the contraction would be altered in the carotid arteries obtained from spontaneously hypertensive rats (SHR) compared to control Wistar Kyoto (WKY) rats. In the carotid arteries from SHR (vs. those from WKY), (1) the 5-HT-mediated contraction was increased, whereas the norepinephrine-mediated contraction was not; (2) 5-HT-mediated contractions were partly inhibited by each kinase (extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase (JNK), PI3K, ROCK, and PDK1) inhibitor; and (3) 5-HT-stimulated phosphorylation of ERK1/2, p38 MAPK, JNK, myosin phosphatase target subunit 1 (MYPT1), and PDK1 was increased. The expression of ROCK2 but not ROCK1 was increased in the carotid arteries from SHR compared to WKY. The expression of 5-HT2A receptor, a major receptor of 5-HT-mediated contraction in rat carotid artery, was similar in carotid arteries between the two groups. These results suggest that 5-HT-mediated contraction was utilized multiple signaling pathways such as ERK1/2, p38 MAPK, JNK, PI3K, ROCK, and PDK1. Although 5-HT-mediated contraction was increased in the carotid arteries obtained from SHR, further studies are necessary to clarify how each kinase may integrate in the vascular smooth muscles under hypertension.
KW - 5-HT
KW - Carotid artery
KW - Contraction
KW - Hypertension
KW - Kinase
KW - PDK1
UR - http://www.scopus.com/inward/record.url?scp=84966706367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84966706367&partnerID=8YFLogxK
U2 - 10.1007/s00424-016-1834-5
DO - 10.1007/s00424-016-1834-5
M3 - Article
C2 - 27170312
AN - SCOPUS:84966706367
SN - 0031-6768
VL - 468
SP - 1271
EP - 1282
JO - Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere
JF - Pflugers Archiv fur die gesamte Physiologie des Menschen und der Tiere
IS - 7
ER -
