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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of atipamezole, detomidine and medetomidine on release of steroid hormones by porcine adrenocortical cells in vitro.

The 4-substituted imidazole type alpha2-adrenoceptor ligands atipamezole, detomidine, and medetomidine were screened for actions on the release of aldosterone by a suspension of porcine adrenocortical cells with deoxycorticosterone (1 microM) as substrate. Progesterone, pregnenolone or corticosterone (all at 1 microM) were also used as substrates. With pregnenolone as substrate, drug-induced effects on the output of nine steroids (aldosterone, corticosterone, cortisol, deoxycortisol, testosterone, progesterone, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone) were monitored simultaneously. The alpha2-adrenoceptor antagonist atipamezole was a potent inhibitor of aldosterone release (range 10-1000 nM). The sedative alpha2-adrenoceptor agonists medetomidine and detomidine also inhibited aldosterone release (range 10-1000 nM). With pregnenolone as substrate, the inhibition induced by 4-substituted imidazoles of the release of corticosterone and cortisol was more pronounced than that of aldosterone. Androstenedione and deoxycortisol release was enhanced. The 4-substituted imidazoles atipamezole, detomidine, and medetomidine inhibited mitochondrial cytochrome P450(11beta/18) in vitro. This inhibition was unrelated to their alpha2-adrenoceptor actions. The 4-substituted imidazole type alpha2-adrenoceptor ligands used to control sedation/anaesthesia can alter the steroid-based defence mechanisms of the body.[1]


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