Sodium nitroprusside (SNP) spontaneously produces nitric oxide (NO). In many cell types, this activates the soluble form of the enzyme guanylyl cyclase (GC), resulting in the elevation of cGMP. We herein report the role of NO and cGMP on iodide uptake in primary cultures of calf thyroid cells. Iodide uptake is the limiting step in thyroid hormone biosynthesis and a typical functional parameter. The effect of SNP on this parameter was thus determined. In cells treated with TSH for 72 h, addition of 5 m SNP for the last 2 h caused a significant inhibition on iodide uptake, with no change in cells not treated with TSH. This action was mimicked by an analogue of cGMP, 8Br-cGMP, and blocked by reduced hemoglobin, thus suggesting that it is mediated by the GC-cGMP pathway. SNP also inhibited the stimulation caused by forskolin or analogues of cAMP, indicating that the effect takes place in this pathway, which would be distal to cAMP generation. The accumulation of radioiodine by thyroid cells is a consequence of the balance between influx and efflux. The studies demonstrate that SNP does not affect iodide efflux, thus revealing that it inhibits the influx.

Iodolipids are the possible mediators of excess iodide in thyroid autoregulation. Previous work from our laboratory has shown that 14-iodo-15-hydroxy-5,8,11 eicosatrienoic acid (I-HO-A) and its omega lactone (IL-w) mimic the inhibitory action of excess iodide upon several parameters of thyroid metabolism. The present experiments were performed in order to study the mechanism of the inhibitory effect of I-HO-A and IL-w on 2-deoxy-D-glucose (DOG) and aminoisobutyric acid (AIB) uptake by calf slices. I-HO-A, IL-w and KI 0.1 mM caused a 33, 31 and 25% inhibition, respectively, of AIB uptake. The presence of 0.1 mM methimazole (MMI) only reversed the effect of KI. The transport of DOG was inhibited by both compounds: I-HO-A caused a 62% decrease, while IL-w produced a 64% inhibition; and MMI failed to relieve their action. On the contrary, the 33% inhibition caused by KI disappeared when MMI was present. Taking into account that AIB and DOG transport across the membrane requires energy, supplied by Na-K-ATPase, changes in its activity were studied. TSH (10 mU/ml) produced a 74% increase in the enzyme activity which was significantly blocked by KI (82%), I-HO-A (100%) and IL-w (100%). Basal enzyme activity was impaired by IL-w (33%), but not by KI. These results were correlated with the decrease of DOG uptake produced by 1 mM ouabain. Tissue specificity effect of iodoarachidonates was demonstrated by the absence of action on DOG transport in kidney and liver.(ABSTRACT TRUNCATED AT 250 WORDS)