Inhibitory action of hydralazine on catecholamine-synthesizing enzymes prepared from bovine adrenal medulla.
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概要
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The direct effect of hydralazine on catecholamine-synthesizing enzymes was investigated. Hydralazine caused a concentration-dependent inhibition of tyrosine hydroxylase (TH) prepared from bovine adrenal medulla, and a more pronounced effect was obtained by incubating the enzyme with the drug prior to the enzyme assay. Kinetic studies showed that hydralazine increased the apparent K<SUB>m</SUB> value of the enzyme for tyrosine and cofactor, 6, 7-dimethyl-5, 6, 7, 8-tetrahydropterin (DMPH<SUB>4</SUB>), without any change in the V<SUB>max</SUB>. The inhibitory effect of the drug was irreversible, and an excess amount of FeSO<SUB>4</SUB> failed to restore the enzyme activity inhibited by this drug. Furthermore, hydralazine also inhibited the dopamine β-hydroxylase (DBH) in chromaffin granule membranes. Hydralazine increased the apparent K<SUB>m</SUB> value of DBH for ascorbic acid without any change in the V<SUB>max</SUB>, and it decreased the V<SUB>max</SUB> of the enzyme for tyramine with no change in the apparent K<SUB>m</SUB> value. The observations described here suggest the possibility that hydralazine presumably causes the inhibition of catecholamine-synthesizing enzymes as a result of allosteric alterations in the molecular structures of these enzymes. It thus seems unlikely that the inhibitory action of hydralazine on these enzymes may totally be based on its metal-chelating activity.
- 公益社団法人 日本薬理学会の論文
著者
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Houchi Hitoshi
Department Of Pharmacology The University Of Tokushima School Of Medicine
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Minakuchi Kazuo
Department Of Clinical Pharmacy Institute Of Health Biosciences The University Of Tokushima Graduate
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Morita Kyoji
Department Of Pharmacology Tokushima University School Of Medicine
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Nakanishi Atsushi
Department Of Radiology Juntendo University
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OKA Motoo
Department of Pharmacology II, Osaka University School of Medicine
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NAKANISHI Atsushi
Department of Pharmacology, Tokushima University School of Medicine
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