Cyclosporin A inhibits angiotensin II-induced c-Jun NH(2)-terminal kinase activation but not protein synthesis in vascular smooth muscle cells

Eur J Pharmacol. 2002 May 17;443(1-3):47-50. doi: 10.1016/s0014-2999(02)01587-x.

Abstract

Angiotensin II activates three major mitogen-activated protein kinases (MAPK) in vascular smooth muscle cells. Although other angiotensin II-induced MAPKs activation require transactivation of a growth factor receptor, the detailed mechanism by which angiotensin II activates c-Jun NH(2)-terminal kinase (JNK) remains unclear. Here, an immunosuppressant, cyclosporin A but not FK506, selectively inhibited angiotensin II-induced JNK activation in vascular smooth muscle cells. However, cyclosporin A had no inhibitory effect on angiotensin II-induced protein synthesis. Thus, angiotensin II-induced JNK activation but not protein synthesis is mediated by a mechanism sensitive to cyclosporin A, which is independent from calcineurin in vascular smooth muscle cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology*
  • Animals
  • Anisomycin / pharmacology
  • Aorta, Thoracic
  • Cells, Cultured
  • Cyclosporine / pharmacology*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Immunosuppressive Agents / pharmacology*
  • JNK Mitogen-Activated Protein Kinases
  • Leucine / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Phosphorylation
  • Protein Biosynthesis*
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology
  • Tacrolimus / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Protein Synthesis Inhibitors
  • Sulfonamides
  • Angiotensin II
  • W 7
  • Anisomycin
  • Cyclosporine
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Leucine
  • Tacrolimus