A study was made of the effect of the administration of reserpine and parachlorophenylalanine, an inhibitor of 5-hydroxytryptamine (serotonin; 5-HT), on the capacity of thyroid parafollicular cells to synthesize and store 5-HT. The two drugs were given to nonhibernating bats in doses which produced an equivalent degree of depletion of 5-HT from the thyroid. Tritiated 5-hydroxytryptophan, the precursor of 5-HT, was then given intravenously to assess the ability of parafollicular cell granules to take up and retain newly synthesized 5-HT. Reserpine, but not parachlorophenylalanine, decreased the amount of labeled 5-HT found in the thyroid and prevented autoradiographic labeling of parafollicular cell granules. Quantitative ultrastructural and stereological analysis demonstrated that the granules in untreated animals appeared to be nearly spherical prolate ellipsoids, with a uniformly electron-opaque inner matrix. In animals given reserpine, the axial ratio of the ellipsoidal granules increased greatly and a faint internal striation parallel to the long axis of the granules became apparent. Similar changes were not induced by parachlorophenylalanine. No other morphological changes in the thyroid epithelium were detected after administration of reserpine. This study confirms the association of 5-HT with the mature small secretory granules of thyroid parafollicular cells.

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