His-Arg-Trp potently attenuates contracted tension of thoracic aorta of Sprague-Dawley rats through the suppression of extracellular Ca2+ influx

Mitsuru Tanaka, Shimpei Watanabe, Zhengquan Wang, Kiyoshi Matsumoto, Toshiro Matsui

研究成果: Contribution to journalArticle査読

22 被引用数 (Scopus)

抄録

In the present study, we primarily attempted to identify di- and tri-peptides showing potent vasodilation in 1.0 μM phenylephrine-contracted thoracic aortas of Sprague-Dawley rats. Synthetic 15 Trp-His (WH) skeleton analogues were used for rat aorta ring's force measurements, since WH was found to be a vasoactive di-peptide so far. Among the synthesized peptides consisted of both His and Trp amino acid residues, His-Arg-Trp (HRW) was found to evoke the most potent vasodilation with an EC50 value of 1.2 ± 0.08 mM in an endothelium-independent manner, while no effect was evoked by a mixture of individual amino acids. In addition to the structure of tri-peptides-activity relationship, chemically modified HRW analogues, i.e., 1- or 3-methyl-His-Arg-Trp and His-citrulline-Trp demonstrated the structural importance of tri-peptide to evoke the vasoactivity as following factors: (1) Neutral imidazole and indole groups from His and Trp residues at N- and C-terminals, respectively and (2) basic amino acids at the middle position. In mitogen (10 μM angiotensin II or 50 μM Bay K8644)-stimulated vascular smooth muscle cells, vasoactive HRW (100 μM) caused significant [Ca2+]i reduction to an extent of >30%. Thus, our results suggest that HRW caused vasodilation action via an endothelium-independent mechanism which probably involves the suppression of extracellular Ca2+ influx through voltage-gated l-type Ca2+ channel.

本文言語英語
ページ(範囲)1502-1507
ページ数6
ジャーナルPeptides
30
8
DOI
出版ステータス出版済み - 8 2009

All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学
  • 内分泌学
  • 細胞および分子神経科学

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