Trapidil inhibits platelet-derived growth factor-induced migration via protein kinase A and RhoA/Rho-associated kinase in rat vascular smooth muscle cells

Kenji Ishikura, Hisayo Fujita, Mariko Hida, Midori Awazu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Trapidil suppresses platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (VSMC) proliferation by inhibiting Raf-1/extracellular signal-regulated kinase (ERK) via cAMP/protein kinase A (PKA). We examined whether trapidil inhibits PDGF-induced VSMC migration and investigated its mechanisms of action. VSMC migration was inhibited to a similar extent by trapidil and forskolin. A PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5- isoquinolinesulfonamide (H89) blocked the inhibition by forskolin to a greater degree than that by trapidil. Trapidil but not forskolin suppressed PDGF-stimulated RhoA activation. In the presence of both H89 and (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride monohydrate, an inhibitor of Rho-associated kinase (ROCK), trapidil and forskolin inhibited migration to a similar extent. Thus, in addition to cAMP/PKA activation, trapidil inhibits RhoA/ROCK activation, which may be important in trapidil's inhibitory effect on migration.

Original languageEnglish
Pages (from-to)28-33
Number of pages6
JournalEuropean Journal of Pharmacology
Volume515
Issue number1-3
DOIs
Publication statusPublished - 2005 May 16

Fingerprint

Trapidil
rho-Associated Kinases
Platelet-Derived Growth Factor
Cyclic AMP-Dependent Protein Kinases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Colforsin
Cell Movement
Mitogen-Activated Protein Kinase 3
Protein Kinase Inhibitors
Cell Proliferation

Keywords

  • Angioplasty
  • Forskolin
  • Protein-serine-threonine kinase
  • Rho GTP-binding protein
  • Trapidil

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Trapidil inhibits platelet-derived growth factor-induced migration via protein kinase A and RhoA/Rho-associated kinase in rat vascular smooth muscle cells. / Ishikura, Kenji; Fujita, Hisayo; Hida, Mariko; Awazu, Midori.

In: European Journal of Pharmacology, Vol. 515, No. 1-3, 16.05.2005, p. 28-33.

Research output: Contribution to journalArticle

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