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

  • Ishikura K
  • Fujita H
  • Hida M
 et al. 
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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. © 2005 Elsevier B.V. All rights reserved.

Author-supplied keywords

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

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Authors

  • Kenji Ishikura

  • Hisayo Fujita

  • Mariko Hida

  • Midori Awazu

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