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 language | English (US) |
|---|---|
| Pages (from-to) | 28-34 |
| Number of pages | 7 |
| Journal | Prostaglandins and Other Lipid Mediators |
| Volume | 80 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jul 2006 |
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Keywords
- Arachidonic acid
- Carbacyclin
- Cytochrome P450
- Miconazole
- PGI
- Smooth muscle cells
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
Inhibition of PGI2 signaling by miconazole in vascular smooth muscle cells. / Zhou, Wei; Lu, Tong D; Spector, Arthur A.; Lee, Hon Chi.
In: Prostaglandins and Other Lipid Mediators, Vol. 80, No. 1-2, 07.2006, p. 28-34.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of PGI2 signaling by miconazole in vascular smooth muscle cells
AU - Zhou, Wei
AU - Lu, Tong D
AU - Spector, Arthur A.
AU - Lee, Hon Chi
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - Arachidonic acid
KW - Carbacyclin
KW - Cytochrome P450
KW - Miconazole
KW - PGI
KW - Smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=33745806593&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745806593&partnerID=8YFLogxK
U2 - 10.1016/j.prostaglandins.2006.03.005
DO - 10.1016/j.prostaglandins.2006.03.005
M3 - Article
C2 - 16846784
AN - SCOPUS:33745806593
VL - 80
SP - 28
EP - 34
JO - Prostaglandins
JF - Prostaglandins
SN - 1098-8823
IS - 1-2
ER -