The biochemistry, physiology, and pharmacology of biogenic amines, amino acid precursors and metabolic products, and various synthetic derivatives have been investigated. The general areas of study include the effects of fluorine substitution on the properties of biogenic amines, adrenergic antagonists and amino acids and catechol-O-methyltransferase (COMT). Studies specific to fluorine substituted compounds include 1) determination of the adrenergic properties of 2- and 6-fluoro derivatives of dopamine, fluoro-alprenolols, fluoro-practolols 2) mechanism of toxicity of 6-fluoro and 2,6-difluorophenylalanine, 6-fluoro-, 2,3-, 2,5-, 2-6-difluorotyrosine and 2-azidotyrosine in cultured pheochromocytoma (PC12) cell lines. Studies on COMT include: 1) immunohistochemical localization of COMT in the luminal and glandular epithelium of rat uterus during estrus, diestrus, pregnancy, pseudopregnancy, postpartum and following ovariectomy in animals treated with and without exogenous progesterone or progesterone-receptor antagonists 2) localization of COMT and macrophage-specific antigens in macrophages of corpora lutea of rat 3) localization of COMT in the rodent and human intestinal track 4) localization of the site of O-methylation in the dental pulp of rat 5) substrate specificity and reaction kinetics of a series of 3'-hydroxycoclaurines and 3'-hydroxy-N-methylcoclaurines as putative precursors of mammalian opioids 6) confirmation of the primary sequence of peptides isolated from the 23KD form of rat liver soluble COMT and preparation of monoclonal antibodies from COMT-specific peptides. Other studies include the irreversible inhibition of brain monoamine oxidase A and B by the binding the isothiocyanates of procaine and proparacaine and the effect of nerve growth factor (NGF) on the uptake of calcium and release of adrenergic neurotransmitters in PC12 cells.
