Mechanism of inhibition of dopamine beta-hydroxylase evoked by FLA-63. An in vitro study.
Bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA-63) inhibits in vitro purified bovine adrenal medullary dopamine beta-hydroxylase (BDH) concentration-dependently; 50% inhibition is produced by 2 x 10(-6)M FLA-63. Spectrophotometric experiments show that FLA-63 is reduced by ascorbate very likely to the corresponding dithiocarbamate-derivative, which acts as a Cu++-chelator. Cu++-ions are able to completely abolish the inhibition of the DBH caused by FLA-63 in concentrations up to 2.5 x 10(-6)M. It is concluded that FLA-63 inhibits the DBH mainly in its reduced form via the formation of a chelate-complex with copper ions derived from the DBH.
D000313:Adrenal Medulla / Q000201:enzymology; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology*; D002417:Cattle; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors
D007093:Imidazoles; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase