Inhibition of rat renal and testicular 11 beta-hydroxysteroid dehydrogenase by some antihypertensive drugs, diuretics, and epitestosterone.
With regard to previous finding of an inhibitory activity of furosemide on 11 beta-hydroxysteroid dehydrogenase, 16 other commonly used diuretics have been tested as to their ability to inhibit rat renal, and in four instances also testicular 11 beta-hydroxysteroid dehydrogenase, using glycerrhetinic acid as a standard. In addition, epitestosterone has been tested as well, with respect to its recently demonstrated inhibitory activity on several other enzymes of androgen biosynthesis. Besides corticosterone, 11 beta-hydroxy-4-androstene-3,17-dione has been used as a substrate. Of all drugs studied, quinapril, dihydralazin, trandolapril, metipamid, methyldopa, betaxolol only appeared to be weak inhibitors of 11 beta-hydroxysteroid dehydrogenase, with an inhibitory activity 10-28% of that of glycyrrhetinic acid. Using corticosterone as a substrate, epitestosterone displayed a weak inhibitory activity with Ki 850, 1200 nmol/l and Vmax 2420, 3900 nmol/l.min for renal and testicular enzyme, respectively. In contrast to kidneys, the testicular 11 beta-hydroxysteroid dehydrogenase accepted also 11 beta-hydroxy-4-androstene-3,17-dione as a substrate, which could be inhibited by epitestosterone (Ki 1490 nmol/l, Vmax 1150 nmol/l.min). The results represent further evidence for different substrate specificity of renal and testicular 11 beta-hydroxysteroid dehydrogenase.
Bicíková
M
M
Institute of Endocrinology, Prague, Czech Republic.
Hill
M
M
Hampl
R
R
Stárka
L
L
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004845:Epitestosterone / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008861:Microsomes / Q000201:enzymology; D051381:Rats; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology*
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D000735:Androstenedione; D004845:Epitestosterone; C003582:11-hydroxyandrostenedione; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003345:Corticosterone