Protein kinase C inhibitors decrease endothelin ET(B) receptor mRNA expression and contraction during organ culture of rat mesenteric artery

Eur J Pharmacol. 2002 Oct 4;452(2):215-22. doi: 10.1016/s0014-2999(02)02303-8.

Abstract

The effect of protein kinase C (PKC) inhibitors on the induction of endothelin ET(B) receptors during organ culture was examined in isolated segments of the rat mesenteric artery. After 24 h of organ culture, the endothelin ET(B) receptor agonist sarafotoxin 6c (S6c) induced a strong contraction compared to fresh segments. The contractile response after 24-h organ culture to S6c was studied in presence (30-min preincubation) or absence, after 24-h treatment, of the PKC inhibitors staurosporine, K252a and Ro31-7549. Exposure to staurosporine or K252a in presence and after 24-h treatment reduced the S6c contraction. In contrast, presence of 2-1[1-3(aminopropyl)indol-3-yl]-3(1-methyl-1H-indol-3-yl)maleimide (Ro31-7549), did not affect the S6c-induced contraction, whereas 24-h treatment abolished the increase of contraction. The PKA inhibitor N-(2-[bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide (H89) did not affect the S6c responses. The mRNA expressions of endothelin ET(B) receptors (analysed with real-time PCR) were abolished after 24-h treatment with the PKC inhibitors. These results suggest that PKC is involved in the endothelin ET(B) receptor upregulation following organ culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Male
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / metabolism
  • Organ Culture Techniques
  • Protein Kinase C / antagonists & inhibitors*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Inbred WKY
  • Receptor, Endothelin B
  • Receptors, Endothelin / biosynthesis*
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology

Substances

  • Enzyme Inhibitors
  • RNA, Messenger
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Protein Kinase C