Nitrogenous Compounds Reversibly Inhibit the Adenosine 3',5'-Monophosphate Response to Thyrotropin: This Effect Is Dissociated from Altered Guanine 3',5'- Monophosphate Levels*

Abstract

Nitrogenous compounds were studied for their effect on cGMP levels in the thyroid. Several agents, including sodium nitrite and hydroxylamine, could generate a rise of over 100-fold in cGMP. At a concentration of 20 mM, HN2OH and NaNO2 significantly reduced cAMP levels previously generated by 0.5 mU/ml TSH. If the slices were rinsed and placed in new buffer without the latter nitrogenous compound, the cAMP response to TSH was restored even though intracellular cGMP levels remained elevated. Thus, the counterregulatory effect of these agents on cAMP levels is not correlated with the presence of high levels of cGMP per se. Both the rise in cGMP and the fall in cAMP could still be detected when Ca++ was deleted from the incubation medium, in contrast to other reported stimuli that elevate cGMP levels in the thyroid.