Search for the new compounds which specifically inhibit the Ca2+-independent abnormal contraction of vascular smooth muscle

Sayaka Matsuo; Hiroko Kishi; Fengling Guo; Chen Wang; Yuichi Takada; Saori Miwa; Naoki Morita; Satoru Ohgiya; Masashi Hosokawa; Kazuo Miyashita; Hozumi Kawamichi; Katsuko Kajiya; Dan Xu; Sei Kobayashi

doi:10.14849/psjproc.2007.0_066_2

Proceedings of Annual Meeting of the Physiological Society of Japan

Session ID : 1OB01-2

DOI https://doi.org/10.14849/psjproc.2007.0_066_2

Conference information

Search for the new compounds which specifically inhibit the Ca²⁺-independent abnormal contraction of vascular smooth muscle

*Sayaka Matsuo, Hiroko Kishi, Fengling Guo, Chen Wang, Yuichi Takada, Saori Miwa, Naoki Morita, Satoru Ohgiya, Masashi Hosokawa, Kazuo Miyashita, Hozumi Kawamichi, Katsuko Kajiya, Dan Xu, Sei Kobayashi

Author information

*Sayaka Matsuo
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Hiroko Kishi
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Fengling Guo
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Chen Wang
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Yuichi Takada
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Saori Miwa
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Naoki Morita
Res. Inst. Gen-Based Biofact. AIST, Sapporo, Japan
Satoru Ohgiya
Res. Inst. Gen-Based Biofact. AIST, Sapporo, Japan
Masashi Hosokawa
Lab. Bioresources Chem. Marine Biosci., Grad. Sch Fish. Sci. Hokkaido Univ., Hakodate, Japan
Kazuo Miyashita
Lab. Bioresources Chem. Marine Biosci., Grad. Sch Fish. Sci. Hokkaido Univ., Hakodate, Japan
Hozumi Kawamichi
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Katsuko Kajiya
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Dan Xu
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Sei Kobayashi
Dept. of Mol Physiol. and Med. Bioreg., Grad. Sch. of Med. Yamaguchi Univ., Ube, Japan
Author's Organization：
Innovation Plaza, Hiroshima, JST, Japan

Keywords: eicosapentaenoic acid (EPA), sphingosylphosphorylcholine (SPC), vascular smooth muscle, C²⁺-independent abnormal contraction, new compounds

CONFERENCE PROCEEDINGS FREE ACCESS

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Abstract

Rho-kinase (ROK)-mediated Ca²⁺-independent abnormal contraction of vascular smooth muscle (VSM) plays an essential role in the pathophysiology of the vasospasm which causes vascular diseases. As an important signaling molecule of vasospasm, we previously identified sphingosylphosphorylcholine (SPC), which activated ROK through the activation of Src family tyrosine kinase (Src-TK) and induced Ca²⁺-independent contraction of VSM. Moreover, we found that eicosapentaenoic acid (EPA) can selectively inhibit such abnormal events without affecting Ca²⁺-dependent normal contraction of VSM. However, EPA is limited to oral administration and thus unsuitable for clinically serious patients unable to ingest orally. We therefore screened the new compounds which are capable to be administrated intravenously that could substitute for EPA. Tension study of VSM showed that several compounds inhibited the SPC-induced abnormal contraction of VSM, and their inhibitory effects were comparable to EPA's. These results suggest that newly found compounds would be the candidates for novel therapeutic drugs capable to be administrated intravenously for vasospasm which could substitute for EPA. [J Physiol Sci. 2007;57 Suppl:S66]

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