The chemistry, biochemistry, physiology, and pharmacology of biogenic amines, their amino acid precursors and metabolic products, and various synthetic derivatives thereof have been investigated. The areas of specific interest are: 1) Elucidation of the primary sequence of areas catechol-O- methyltransferase(COMT) and construction of a COMT-specific cDNA probe, 2) The immunohistochemical localization of COMT in malignant, physiologically and hormonally modified, and normal tissues from rodent, and human at the light and electron microscopic level including the following: Examination of the temporal and hormonal relationship between uterine epithelial COMT during the course of pregnancy in golden hamster; study of the relationship between breast adenocarcinoma in woman; COMT levels in gynomasty in man; and an examination of the distribution of catechol estrogens and COMT in parotid gland and anterior pituitary of rat, 3) A study of the chemical and biological properties of various fluoro derivatives of biogenic amines, amino acids, and related compounds including studies of the following: The electrochemical, redox properties and electron densities of fluorocatechols; the interaction of fluorophenylephrines and fluoroepinephrines with both alpha and beta receptor systems; the interaction at the active site of COMT; the uptake and metabolism of 6-fluorodopa and 6-fluorodihydroxyphenylserine in vitro and in vivo; the application of fluorine-18 analogs of dopa and dihydroxypehnylserine as PETT scanning agents for dopamine and norepinephrine neurons in the intact animal; and the uptake and mechanism of toxicity of 6-fluorodopa, 2,6-fluorodopa, 6- fluorotyrosine and 2,6-difluorotyrosine in cultured pheochromocytoma and melanoma cell lines.
