Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost-induced vasorelaxation and cyclic AMP elevation in isolated guinea-pig aorta

Br J Pharmacol. 1999 Feb;126(4):845-7. doi: 10.1038/sj.bjp.0702383.

Abstract

The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and increases cyclic AMP, although the relationship between adenosine 3': 5'-cyclic monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore investigated the effect of the adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) on iloprost-mediated relaxation and cyclic AMP elevation in endothelium-denuded aortic strips. Iloprost (1-1000 nM) caused a concentration-dependent inhibition of phenylephrine (1-6 microM) contractions, the responses being unaffected by pre-incubation with SQ22536 (100 microM) for 30 min. In other experiments 60 nM iloprost caused a 64% inhibition of phenylephrine contractions concomitant with a 3 fold rise in cyclic AMP. SQ22536 completely abolished the iloprost-induced elevation in cyclic AMP while having no significant effect on relaxation. Our results therefore strongly suggest that cyclic AMP-independent pathways are responsible for the vasorelaxant effects of iloprost in guinea-pig aorta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Adenylyl Cyclase Inhibitors*
  • Animals
  • Aorta / drug effects*
  • Aorta / physiology
  • Cyclic AMP / physiology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Guinea Pigs
  • Iloprost / pharmacology*
  • In Vitro Techniques
  • Male
  • Vasodilation / drug effects*

Substances

  • Adenylyl Cyclase Inhibitors
  • Enzyme Inhibitors
  • 9-(tetrahydro-2-furyl)-adenine
  • Cyclic AMP
  • Adenine
  • Iloprost