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Abstract
The in vitro spasmolytic activity of glycerol trinitrate was measured on the KCl-contraction
of aorta strips from the rabbit. In the presence of sulphobromophthalein, a known
inhibitor of glutathione S-transferase, the dose-activity curve for the nitrate was
displaced to the right. Much smaller displacements were obtained with the control
spasmolytic substances--papaverine and S-nitroso-N-acetylpenicillamine. It was confirmed
that sulphobromophthalein inhibits glutathione S-transferase activity in aorta homogenates.
Aorta extracts did not detectably catalyze the reaction between glutathione and sulphobromophthalein
and the glutathione level was not decreased by treating the intact aorta with sulphobromophthalein.
It is concluded that sulphobromophthalein acts as a specific antagonist of the spasmolytic
activity of glycerol trinitrate, probably as a result of its inhibition of glutathione
S-transferase. It thus seems probable that glutathione and glutathione S-transferase
are involved in the pharmacological activation of the organic nitrates.