Regulation of cardiovascular functions by the phosphorylation of TRPC channels

Motohiro Nishida, Shota Saiki, Naoyuki Kitajima, Michio Nakaya, Yoji Sato, Hitoshi Kurose

研究成果: Contribution to journalReview article査読

2 被引用数 (Scopus)

抄録

Calcium ions (Ca2+) play an essential role in homeostasis and the activity of cardiovascular cells. Ca2+ influx across the plasma membrane induced by neurohumoral factors or mechanical stress elicits physiologically relevant timing and spatial patterns of Ca2+ signaling, which leads to the activation of various cardiovascular functions, such as muscle contraction, gene expression, and hypertrophic growth of myocytes. A canonical transient receptor potential protein subfamily member, TRPC6, which is activated by diacylglycerol and mechanical stretch, works as an upstream regulator of the Ca2+ signaling pathway required for pathological hypertrophy. We have recently found that the inhibition of cGMP-selective phosphodiesterase 5 (PDE5) suppresses agonist- and mechanical stretch-induced hypertrophy through inhibition of Ca2+ influx in rat cardiomyocytes. The inhibition of PDE5 suppressed the increase in frequency of Ca2+ spikes induced by receptor stimulation or mechanical stretch. Activation of protein kinase G by PDE5 inhibition phosphorylated TRPC6 proteins at Thr69 and prevented TRPC6-mediated Ca2+ influx. Substitution of Ala for Thr69 in TRPC6 abolished the antihypertrophic effects of PDE5 inhibition. These results suggest that phosphorylation and functional suppression of TRPC6 underlies the prevention of cardiac hypertrophy by PDE5 inhibition. As TRPC6 proteins are also expressed in vascular smooth muscle cells and reportedly participate in vascular remodeling, TRPC6 blockade may be an effective therapeutic strategy for preventing pathologic cardiovascular remodeling.

本文言語英語
ページ(範囲)1427-1433
ページ数7
ジャーナルYakugaku Zasshi
130
11
DOI
出版ステータス出版済み - 11 2010

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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