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Abstract

Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.

Z Huszti and T L Sourkes
Journal of Pharmacology and Experimental Therapeutics February 1975, 192 (2) 432-440;
Z Huszti
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T L Sourkes
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Abstract

Measurements of the rate of expiration of 14CO2 were carried out after the injection into rats of 14C-histidine labeled in the carboxyl group (C-His) or in the imidazole ring (R-His). Intraperitoneal administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, a new potent inhibitor of histidine decarboxylase, reduced the rate of 14CO2 production from C-His and R-His in a dose-dependent manner. The metabolism of C-His was more affected than that of R-His. The inhibitor had no effect on the production of 14CO2 from 14C-urocanic acid, 14C-dopa or 14C-glutamic acid. Rats given 2-hydroxy-5-carbomethoxybenzyloxyamine (100 mg/kg) by the intraperitoneal route had diminished histidine decarboxylase activity of stomach (96 percent decrease), but did not have any change in the activities of histidase, urocanase or histidine-pyruvate aminotransferase of liver. After the administration of histidine (500 mg/kg), the level of this amino acid in serum remained elevated somewhat longer in inhibitor-treated animals than in the controls. The temporary rise in serum histidine relative to controls that were also histidine-loaded is considered to reflect the decreased rate of uptake of histidine into the tissues, and also a decreased rate of decarboxylation of histidine in certain organs. After the administration of 2-hydroxy-5-carbomethoxybenzyloxyamine, the decreased rate of 14CO2 production from injected R-His and the delayed disappearance of histidine from the serum after a histidine load were considered to reflect mainly the decreased rate of histidine uptake into the tissues. The decreased rate of formation of 14CO obtained with C-His appeared to result from inhibition of both uptake and decarboxylation of histidine.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 192, Issue 2
1 Feb 1975
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Abstract

Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.

Z Huszti and T L Sourkes
Journal of Pharmacology and Experimental Therapeutics February 1, 1975, 192 (2) 432-440;

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Abstract

Inhibition of histidine, decarboxylation in vivo by 2-hydroxy-5-carbomethoxybenzyloxyamine, a new, potent inhibitor of histidine decarboxylase.

Z Huszti and T L Sourkes
Journal of Pharmacology and Experimental Therapeutics February 1, 1975, 192 (2) 432-440;
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