Inhibitory Effects of Different Retinoids (Vitamin A Analogues) on the Stimulated Rat Liver Guanylate Cyclase Activity

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Abstract
Vitamin A and its analogues show the ability to prevent malignant cell transformation on induction with different carcinogens, such as nitrosamines. Cyclic GMP has been proposed as a positive modulator of malignant cell growth and the cGMP‐forming enzyme guanylate cyclase is strongly stimulated by e.g. nitrosamines. In this study, we found that retinylacetate and retinal were very potent inhibitors of the stimulated guanylate cyclase. When a series of structurally different retinoids were tested in the same system, a wide range of inhibitory activity on guanylate cyclase was found for the different retinoids with some being completely ineffective. The most potent inhibitor was retinylacetate. Furthermore, the inhibitory profile of the retinoids on the guanylate cyclase did not seem to correlate to their in vivo activity as antineoplastic agents, as described in the literature. We therefore conclude that there does not exist a general connection between the anticancer activity and the guanylate cyclase inhibition of the retinoids. However, it can not be excluded that the guanylate cyclase inhibition might be of importance for the antineoplastic activity for some of the retinoids.