Some histamine-related compounds interacting with the benzylamine-oxidizing activity of rat white adipocytes.
In rat white adipocytes histamine is oxidized by a semicarbazide-sensitive amine oxidase which has benzylamine or preferential substrate (Bz-SSAO). To determine whether Bz-SSAO could control the extracellular levels of histamine and other histamine-related compounds active in lipid mobilization, a series of histaminergic compounds was screened as possible substrates or inhibitors of Bz-SSAO activity. Histaminergic compounds with imidazolo or thiazolo groups are oxidized by rat white-adipocyte Bz-SSAO whereas S-isothiourea derivatives, with two- or three-carbon-atom alkyl chains between the isothiourea and the N,N-dimethyl residue are, instead, inhibitors of the enzyme. Amtamine has been identified as a selective, high affinity substrate for rat white adipocyte Bz-SSAO. This enzymatic degradation might represent a catabolic pathway for the drug. These results show that the histaminase property of the rat white-adipocyte enzyme Bz-SSAO also extends to other histamine derivatives active at histamine receptors.
Raimondi
L
L
Department of Pharmacology, University of Florence, Italy.
Conforti
L
L
Banchelli
G
G
Sgromo
L
L
Pirisino
R
R
D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001596:Benzylamines / Q000378:metabolism*; D002478:Cells, Cultured; D003956:Dialysis; D006632:Histamine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D001596:Benzylamines; D008996:Monoamine Oxidase Inhibitors; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D013890:Thiourea