Tissue histopathology, clinical chemistry and behaviour of adult comt‐gene‐disrupted mice

Catechol‐O‐methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O‐methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen‐dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt‐gene‐disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen‐dependent organs such as mammary glands and uterus.

[1]  R. Weinshilboum,et al.  Human monoamine oxidase. Lack of brain and platelet correlation. , 1986, Archives of general psychiatry.

[2]  O. Suchowersky,et al.  COMT Inhibitors in Parkinson's Disease , 1999, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[3]  H. H. Keller,et al.  Short-acting novel MAO inhibitors: In vitro evidence for the reversibility of MAO inhibition by moclobemide and Ro 16-6491 , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[4]  F. Assal,et al.  Tolcapone and fulminant hepatitis , 1998, The Lancet.

[5]  M. Koulu,et al.  Plasma 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are insensitive indicators of alpha 2-adrenoceptor mediated regulation of norepinephrine release in healthy human volunteers. , 1991, Life sciences.

[6]  D. Bell,et al.  An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. , 1997, Cancer research.

[7]  P. Seeman,et al.  Dopamine receptors and transporters in Parkinson's disease and schizophrenia , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  M. Kuhar,et al.  Dopamine transporter: Solubilization from dog caudate nucleus , 1989, Synapse.

[9]  M. Koulu,et al.  Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers. , 1989, British journal of clinical pharmacology.

[10]  C. Frith,et al.  Hematologic and clinical chemistry findings in control BALB/c and C57BL/6 mice. , 1980, Laboratory animal science.

[11]  B. Emanuel,et al.  Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1----q11.2. , 1992, Genomics.

[12]  D. Pfaff,et al.  Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C. Warren Olanow,et al.  Tolcapone and Hepatotoxic Effects , 2000 .

[14]  M. Karayiorgou,et al.  Brain catecholamine metabolism in catechol‐O‐methyltransferase (COMT)‐deficient mice , 2002, The European journal of neuroscience.

[15]  F. Gohs,et al.  Reference range data base for serum chemistry and hematology values in laboratory animals. , 1986, Journal of toxicology and environmental health.

[16]  G. Peterson,et al.  A simplification of the protein assay method of Lowry et al. which is more generally applicable. , 1977, Analytical biochemistry.

[17]  I. Kopin,et al.  Catecholamine metabolism: basic aspects and clinical significance. , 1985, Pharmacological reviews.

[18]  A. Conney,et al.  Functional role of estrogen metabolism in target cells: review and perspectives. , 1998, Carcinogenesis.

[19]  I. Ulmanen,et al.  Distribution of catechol-O-methyltransferase enzyme in rat tissues. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[20]  P. Männistö,et al.  Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. , 1999, Pharmacological reviews.

[21]  G. Gerhardt,et al.  Clearance of Exogenous Dopamine in Rat Dorsal Striatum and Nucleus Accumbens: Role of Metabolism and Effects of Locally Applied Uptake Inhibitors , 1993, Journal of neurochemistry.

[22]  C. Marsden,et al.  Catechol-O-methyl transferase: pharmacological aspects and physiological role. , 1975, Pharmacological reviews.

[23]  J. Freudenheim,et al.  Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. , 1998, Cancer research.

[24]  P. Tuomainen,et al.  Different in vivo properties of three new inhibitors of catechol O‐methyltransferase in the rat , 1992, British journal of pharmacology.

[25]  M. Karayiorgou,et al.  Effect of Dopamine Uptake Inhibition on Brain Catecholamine Levels and Locomotion in Catechol-O-methyltransferase-Disrupted Mice , 2002, Journal of Pharmacology and Experimental Therapeutics.

[26]  S. Handley,et al.  Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour , 1984, Naunyn-Schmiedeberg's Archives of Pharmacology.