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Effect of anti-inflammatory drugs on glucosamine-6-phosphate synthetase from inflamed tissue of rats.

1) The in vitro synthesis of glucosamine-6-phosphate (Gm-6-P) was inhibited effectively by adding aurothiomalate and acid non-steroidal anti-inflammatory drugs to the incubation mixtures. The drug-action was more sensitive in the reaction with the supernatant fluid of the croton oil-induced granulation tissue homogenate using as a source of Gm-6-P synthetase, as compared to the case of the liver homogenate. Potency of each compound was in the following descending order ; aurothiomalate, flufenamic and mefenamic acids, phenylbutazone and salicylic acid. Chloroquine and aminopyrine had no effect on Gm-6-P synthesis with the enzymes from both sources at 10-3M. 2) A markedly high activity of Gm-6-P synthetase was found in the swollen hind paws of the rats which were suffered from adjuvant disease. pH-difference was seen in the maximum production of Gm-6-P between the inflamed tissue and liver enzymes. The optimum pH was 6.8 for the reaction with the homogenates of the swollen paws and croton oil-induced granulation tissue, while that for the liver enzyme was in the range from 7.7 to 8.3. 3) Good correlation was seen between increases of the enzyme activity and the swelling in the hind paws as adjuvant disease appeared and developed in rats. On the other hand, the activity of the liver enzyme was not changed significantly by the development of the typical inflammatory lesions. 4) The drug-action to Gm-6-P synthesis with the paw enzyme was much clearer in the reaction at pH 6.8 than pH 7.7.