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Studies on the inhibition of histidine decarboxylase, aromatic-l-amino acid decarboxylase and acid secretion by brocresine and its metabolites

1973; Elsevier BV; Volume: 22; Issue: 8 Linguagem: Inglês

10.1016/0006-2952(73)90218-9

1873-2968

Leon Ellenbogen, Robert G. Kelly, Russell J. Taylor, C.S. Stubbs,

Polyamine Metabolism and Applications

Brocresine (NSD 1055) is rapidly metabolized in vivo. The probable metabolites are 4-bromo-3-hydroxy-benzyl alcohol, 4-bromo-3-hydroxy-benzoic acid and 4-bromo-3-hydroxy-hippuric acid. Brocresine and these metabolites inhibit both rat fetal and rat gastric histidine decarboxylase (l-histidine carboxylase, EC 4.1.1.22) in vitro with a molar I50 of about 10−8, 10−4, lO−3 and 10−5, respectively, for both enzymes. Brocresine and the metabolites also inhibit aromatic-l-amino acid decarboxylase (3,4-dihydroxy-l-phenylalanine carboxylase EC 4.1.1.26) from hog kidney and rat gastric mucosa in vitro with a molar I50 of about 10−7, 10−4, 10−3 and 10−3, respectively, for both enzymes. Brocresine, the alcohol metabolite and the acid metabolite inhibited rat gastric histidine decarboxylase after intraperitoneal administration of 200 mgkg, whereas the hippurate was only weakly inhibitory. All four compounds inhibited gastric acid secretion in the pylorus-ligated rat, but the acid and hippurate were only moderately inhibitory. The reaction of hemoglobin with brocresine to form methemoglobin readily explains the rapid disappearance of the inhibitory activity of the drug.