Ketoconazole inhibition of progesterone oxidation by the rabbit

Senciall, Ian R.; Rahal, S.; Roberts, Roland K.

doi:10.1016/0006-2952(88)90397-8

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…Many inhibitors to CYP isoforms have been determined from biochemical studies with enzyme preparations. Ketoconazole and progesterone, inhibitors selective to CYP3A (Senciall et al ., 1988; Chiba et al ., 1996), were clearly effective in attenuating the response to acetylcholine but were without effect on the SNP‐induced relaxation. Although Ca 2+ ‐activated K + channel blocking actions of ketoconazole and progesterone have been reported in the cells other than vascular smooth muscle cells, the concentration (10 μ M ) of both agents used in the present study is reportedly ineffective (Ishii et al ., 1997; Ehring et al ., 1998).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, debrisoquine, an inhibitor of CYP2D6 (Marre et al ., 1992), and lauric acid, an inhibitor of CYP4A1 (Lawson, 1991), did not significantly reduce the acetylcholine action. The concentrations used are evidenced to be sufficient to inhibit activities of the corresponding CYP isoforms (Chiba et al ., 1996; Senciall et al ., 1988; Iribarne et al ., 1996). These findings indicate a possible involvement of CYP3A product(s) with K + channel opening property in the acetylcholine‐induced relaxation.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery

Ayajiki

Okamura

Fujioka

et al. 1999

British J Pharmacology

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1 In monkey lingual artery strips partially contracted with prostaglandin F 2a , acetylcholineinduced, concentration-related relaxations were abolished by removal of the endothelium. The response was not signi®cantly in¯uenced by indomethacin but attenuated by N G -nitro-L-arginine (L-NOARG); the e ect of the nitric oxide (NO) synthase inhibitor was reversed by L-arginine. 2 The response to acetylcholine resistant to L-NOARG was suppressed in the strips exposed to high K + media. Charybdotoxin partially inhibited the relaxation, and the remaining relaxation was abolished by additional treatment with apamin, whereas glibenclamide, iberiotoxin or apamin alone was without e ect. Relaxations induced by sodium nitroprusside were not in¯uenced by charybdotoxin.3 The L-NOARG-resistant acetylcholine-induced relaxation was inhibited by metyrapone, proadifen and 17-octadecynoic acid, non-selective cytochrome P450 mono-oxygenase (CYP) inhibitors, and progesterone and ketoconazole, inhibitors selective to CYP3A. The inhibitors did not a ect the nitroprusside-induced relaxation. Selective inhibitors of other CYP isoforms, such as debrisoquine and lauric acid, did not reduce the response to acetylcholine. 4 Reaction mixture containing human liver microsome rich in CYPs, arachidonic acid and NADPH incubated at 378C and ®ltrated relaxed endothelium-denuded monkey lingual artery strips, used as bioassay tissues. This response was abolished in the strips exposed to high K + media. The response was also suppressed by combined treatment of the assay tissue with charybdotoxin plus apamin, but was not a ected by treatment with iberiotoxin. The reaction mixture co-incubated with ketoconazole failed to relax the strips. 5 It is concluded that the monkey lingual arterial relaxation dependent on the endothelium is mediated by NO and also by a charybdotoxin plus apamin-sensitive but iberiotoxin-insensitive Ca 2+ -activated K + channel opening substance(s) that may be a CYP3A-derived arachidonic acid metabolite(s).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery

Ayajiki

Okamura

Fujioka

et al. 1999

British J Pharmacology

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Mechanisms underlying endothelium-dependent, nitric oxide- and prostanoid-independent relaxation in monkey and dog coronary arteries

Fujioka

Ayajiki

Shinozaki

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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We compared the mechanisms of vasorelaxation of acetylcholine and of substance P with reference to K(+) channels, and analyzed pharmacologically the nature of endothelium-derived substance(s) other than NO and prostanoids in monkey and dog coronary arteries. Coronary arteries were isolated from monkeys and dogs, and the isometric tension of the artery strips was measured. In canine coronary artery strips treated with indomethacin plus N(G)-nitro- L-arginine ( L-NA) and partially contracted with prostaglandin F(2alpha), acetylcholine induced concentration-related relaxation, which was abolished by removal of the endothelium. The relaxation was markedly suppressed but not abolished in the strips exposed to high K(+) media. Charybdotoxin plus apamin potently inhibited the relaxation to the similar extent to that by high K(+) media, whereas glibenclamide or iberiotoxin had no effect. The relaxation was markedly inhibited by quinacrine, a phospholipase A(2) inhibitor, and ketoconazole, a selective cytochrome P450 (CYP) 3A inhibitor, but not by sulfaphenazole, a selective CYP 2C inhibitor. In contrast to acetylcholine, endothelium-dependent and indomethacin-plus- L-NA-resistant relaxation induced by substance P was not inhibited by high K(+) media, charybdotoxin plus apamin, or ketoconazole. Quinacrine and AA861, a 5-lipoxygenase inhibitor, inhibited the relaxation induced by substance P. In monkey coronary artery, acetylcholine-induced relaxation resistant to indomethacin plus L-NA was abolished by endothelial denudation and by treatment with high K(+) media, charybdotoxin plus apamin, progesterone and ketoconazole, but was not affected by iberiotoxin or sulfaphenazole. Substance P did not relax monkey coronary arteries. It is concluded that endothelium-dependent, nitric oxide- and prostanoid-independent relaxation induced by acetylcholine in monkey and dog coronary arteries are mediated by charybdotoxin plus apamin-sensitive but iberiotoxin-insensitive Ca(2+)-activated K(+) channel opening substance(s), which may be CYP3A-derived arachidonic acid metabolite(s). Contrasting to the response to acetylcholine, endothelium-dependent, indomethacin-plus- L-NA-resistant relaxation induced by substance P in dog coronary artery is not associated with K(+) channel opening, and may be mediated by 5-lipoxygenase product(s).

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Corticosteroid side-chain oxidations—I. Structural effects on the excreted isotope ratios of 4-14C- and 21-3H-labelled corticosteroid metabolites in rabbit urine

Senciall

Rahal

Roberts

1991

The Journal of Steroid Biochemistry and Molecular Biology

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Ketoconazole inhibition of progesterone oxidation by the rabbit

Cited by 6 publications

References 20 publications

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery

Mechanisms underlying endothelium-dependent, nitric oxide- and prostanoid-independent relaxation in monkey and dog coronary arteries

Corticosteroid side-chain oxidations—I. Structural effects on the excreted isotope ratios of 4-14C- and 21-3H-labelled corticosteroid metabolites in rabbit urine

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Ketoconazole inhibition of progesterone oxidation by the rabbit

Cited by 6 publications

References 20 publications

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K+ channel opening substance in monkey lingual artery

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K+ channel opening substance in monkey lingual artery

Mechanisms underlying endothelium-dependent, nitric oxide- and prostanoid-independent relaxation in monkey and dog coronary arteries

Corticosteroid side-chain oxidations—I. Structural effects on the excreted isotope ratios of 4-14C- and 21-3H-labelled corticosteroid metabolites in rabbit urine

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Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery

Involvement of CYP3A‐derived arachidonic acid metabolite(s) in responses to endothelium‐derived K⁺ channel opening substance in monkey lingual artery