Inhibition of PGI2 signaling by miconazole in vascular smooth muscle cells

Wei Zhou, Tong Lu, Arthur A. Spector, Hon Chi Lee

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Miconazole is widely used clinically as an anti-fungal agent and experimentally as a cytochrome P450 (CYP) inhibitor. In rat coronary arteries that produce PGI2 as the major arachidonic acid (AA) metabolite, activation of the large-conductance K+ (BK) channels in coronary arterial smooth muscle cells by AA was inhibited by miconazole but not by the CYP inhibitor SKF525A. Activation of BK currents in coronary smooth muscle cells by carbacyclin or iloprost also was inhibited by miconazole but not by SKF525A, suggesting that miconazole might have properties other than those of CYP inhibition. In addition, carbacyclin-induced dilation of isolated mesenteric arteries was inhibited by treatment with miconazole (51.9 ± 4.2% dilation in control, n = 7 versus 30.1 ± 4.0% with miconazole, n = 4, p < 0.005) but not SKF525A (52.8 ± 3.6%, n = 8). In contrast, miconazole did not affect BK channel activation and vasodilation produced by the phosphodiesterase inhibitor RO-201724. In cultured coronary smooth muscle cells, carbacyclin (1 μM) stimulated cAMP production by 22-fold (183 ± 29 pmol/mg at baseline, 4062 ± 212 pmol/mg with carbacyclin, n = 3, p < 0.001). The carbacyclin effect was significantly attenuated by treatment with miconazole (1542 ± 201 pmol/mg, n = 3, p < 0.001 versus carbacyclin alone), but not by SKF525A (3460 ± 406 pmol/mg, n = 3, p = NS versus carbacyclin alone). These results indicate that in addition to its CYP inhibition properties, miconazole inhibits PGI2 signaling. Hence, experiments using miconazole as a CYP inhibitor should be interpreted with caution.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalProstaglandins and Other Lipid Mediators
Volume80
Issue number1-2
DOIs
StatePublished - Jul 1 2006

Keywords

  • Arachidonic acid
  • Carbacyclin
  • Cytochrome P450
  • Miconazole
  • PGI
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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