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

Authors

  • Sally Turcato,

    1. Centre for Clinical Pharmacology, Wolfson Institute for Biomedical Research, Department of Medicine, UCL, London WC1E 6JJ, England, U.K.
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  • Lucie H Clapp

    Corresponding author
    1. Centre for Clinical Pharmacology, Wolfson Institute for Biomedical Research, Department of Medicine, UCL, London WC1E 6JJ, England, U.K.
      Centre for Clinical Pharmacology, Wolfson Institute for Biomedical Research, Department of Medicine, UCL, London WC1E 6JJ, England, U.K.
    Search for more papers by this author

Centre for Clinical Pharmacology, Wolfson Institute for Biomedical Research, Department of Medicine, UCL, London WC1E 6JJ, England, U.K.

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 μM) contractions, the responses being unaffected by pre-incubation with SQ22536 (100 μM) 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.

British Journal of Pharmacology (1999) 126, 845–847; doi:10.1038/sj.bjp.0702383

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