thiouracil and Pituitary-Neoplasms

6-n-Propyl-2-thiouracil (6-PTU), the antithyroid agent, produces a time-, concentration-, and turnover-dependent inactivation of the NO synthetic capability of the neuronal nitric oxide synthase isoform irreversible by either arginine or (6R)-5,6,7,8-tetrahydro-L-biopterin. By contrast 6-PTU produces an inhibition of the cytokine-inducible and endothelial nitric oxide synthases fully reversible by arginine. The inactivation of neuronal nitric oxide synthase by 6-PTU follows first order kinetics, and is inhibited competitively by both arginine and (6R)-5,6,7,8-tetrahydro-L-biopterin, but is not accompanied by either a loss of heme-CO binding, heme fluorescence, or disassembly of dimeric structure. 2-Thiouracil behaves qualitatively identically to 6-PTU. Turnover-dependent inactivation of neuronal nitric oxide synthase by [2-14C]-2-thiouracil is accompanied by incorporation of radioactivity into the polypeptide chain. Ca2+-dependent NO formation by GH3 pituitary cells is inhibited by 6-PTU in a manner enhanced by depletion of either extracellular arginine or intracellular (6R)-5,6,7,8-tetrahydro-L-biopterin. These observations establish that 6-PTU is an alternate substrate, mechanism-based inactivator of the neuronal nitric oxide synthase isoform with the ability to suppress cellular NO formation.

Topics: Animals; Antithyroid Agents; Arginine; Biopterins; Calcium; Calmodulin; Carbon Monoxide; Carbon Radioisotopes; Citrulline; Enzyme Activation; Enzyme Inhibitors; Heme; Kinetics; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pituitary Neoplasms; Propylthiouracil; Rats; Thiouracil; Tumor Cells, Cultured

Topics: 17-Ketosteroids; Adolescent; Adult; Animals; Estradiol; Estrogens; Female; Follow-Up Studies; Goiter; Humans; Iodine Isotopes; Male; Metabolism, Inborn Errors; Mice; Neoplasm Metastasis; Pituitary Neoplasms; Radiography, Thoracic; Rats; Thiouracil; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adrenal Glands; Amyloidosis; Animals; Antithyroid Agents; Castration; Iodine Isotopes; Kidney; Liver; Mice; Mice, Inbred C3H; Pathology; Pituitary Neoplasms; Propylthiouracil; Research; Spleen; Thiouracil; Thyroid Gland; Thyroid Hormones; Thyrotropin; Toxicology

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Blood; Body Weight; Estradiol; Growth Hormone; Hydrocortisone; Neoplasms; Neoplasms, Experimental; Pharmacology; Pituitary Neoplasms; Prolactin; Rats; Research; Thiouracil; Thymus Gland; Thyroxine

Topics: Animals; Carcinogenesis; Diet; Neoplasms; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Neoplasms; Rats; Thiouracil; Thyroid Gland; Thyrotrophs

Topics: Animals; Mice; Neoplasms; Neoplasms, Experimental; Pituitary Gland; Pituitary Neoplasms; Thiouracil; Thyroid Gland

Topics: Animals; Estrogens; Neoplasms; Neoplasms, Experimental; Pituitary Gland; Pituitary Neoplasms; Rats; Thiouracil; Thiourea; Thyroid Gland; Thyroxine

Topics: Animals; Carcinogens; Mice; Neoplasms; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Neoplasms; Thiouracil

Topics: Animals; Mice; Neoplasms; Neoplasms, Experimental; Pituitary Gland; Pituitary Neoplasms; Propylthiouracil; Thiouracil; Thyroid Gland; Thyroid Neoplasms