Increase of Plasma Uric Acid in Rats Treated with Biogeneamines
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概要
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A possible effect of biogeneamines on the concentration of plasma uric acid in oxonate-treated rats was studied as a model for evaluating drug-induced hyperuricemia. We previously reported that catecholamine stimulated a rapid breakdown of tissue adenine nucleotides, resulting in a marked increase of plasma uric acid and allantoin in rats.The increase of plasma uric acid by catecholamine could be observed more sensitively in oxonate-treated rats, in which further metabolism of uric acid to allantoin was effectively inhibited.<BR>The oxonate-treated rats showed an increase of plasma uric acid not only upon administration of catecholamine, but also with various biogeneamines.<BR>Acetylcholine given through the tail vein of animals caused only a transient increase of plasma uric acid, while its effect was markedly potentiated by pretreatment with cholinesterase inhibitor such as physostigmine. Physostigmine or neostigmine alone also increased plasma uric acid. Carbachol produced a more stable increase of plasma uric acid than acetylcholine, and the increase was obviously abolished by pretreatment with methylatropine, while hexamethonium had no effect on the action of carbachol. Serotonin and histamine also increased plasma uric acid, and their effects were obviously blocked by the administration of cyproheptadine or dimetotiazine, which are well-known blockers of the pharmaclolgical actions of serotonin and histamine.<BR>The increases of plasma uric acid caused by carbachol, serotonin and histamine depended upon their doses and had time courses similar to that caused by catecholamine.<BR>Thus, a number of biogeneamines can play a role in the increase of plasma uric acid. Considering the importance of biogeneamines in the pathogenesis of disease and in treatment with diverse drugs, we should further try to elucidate the induction mechanism of hyperuricemia by each amine.
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