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Catecholamine Synthesis (catecholamine + synthesis)
Selected AbstractsCatecholamine synthesis and metabolism in the central nervous system of mice lacking ,2 -adrenoceptor subtypesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009MA Vieira-Coelho Background and purpose:, This study investigates the role of ,2 -adrenoceptor subtypes, ,2A, ,2B and ,2C, on catecholamine synthesis and catabolism in the central nervous system of mice. Experimental approach:, Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from ,2A -, ,2B - and ,2C -adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice. Key results:, Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in ,2A - and ,2C -adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in ,2A and ,2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; ,2AKO: 6.9 ± 0.7, 1.9 ± 0.1; ,2BKO: 2.3 ± 0.2, 1.0 ± 0.1; ,2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue),1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in ,2A and ,2CKO [WT: 40 ± 1; ,2A: 77 ± 2; ,2B: 40 ± 1; ,2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein),1·h,1], but no significant differences were found in dopamine ,-hydroxylase. Of the catabolic enzymes, catechol- O -methyltransferase enzyme activity was significantly higher in all three ,2KO mice [WT: 2.0 ± 0.0; ,2A: 2.4 ± 0.1; ,2B: 2.2 ± 0.0; ,2C: 2.2 ± 0.0 nmol·(mg protein),1·h,1], but no significant differences were found in monoamine oxidase activity between all ,2KOs and WT mice. Conclusions and implications:, In mouse brain, deletion of ,2A - or ,2C -adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any ,2 -adrenoceptor subtypes resulted in increased activity of catechol- O -methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in ,2A and ,2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. [source] Transgenic expression of Cre recombinase from the tyrosine hydroxylase locusGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2004Jonas Lindeberg Abstract Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3,-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development. genesis 40:67,73, 2004. © 2004 Wiley-Liss, Inc. [source] Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesisJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Larisa Bobrovskaya Abstract Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine synthesis. Its activity is known to be controlled acutely (minutes) by phosphorylation and chronically (days) by protein synthesis. Using bovine adrenal chromaffin cells we found that nicotine, acting via nicotinic receptors, sustained the phosphorylation of TH at Ser40 for up to 48 h. Nicotine also induced sustained activation of TH, which for the first 24 h was completely independent of TH protein synthesis, and the phosphorylation of TH at Ser31. Imipramine did not inhibit the acute phosphorylation of TH at Ser40 or TH activation induced by nicotine, but did inhibit the sustained responses to nicotine seen at 24 h. The protein kinase(s) responsible for TH phosphorylation at Ser40 switched from being protein kinase C (PKC) independent in the acute phase to PKC dependent in the sustained phase. Sustained phosphorylation and activation of TH were also observed with histamine and angiotensin II. Sustained phosphorylation of TH at Ser40 provides a novel mechanism for increasing TH activity and this leads to increased catecholamine synthesis. Sustained phosphorylation of TH may be a selective target for drugs or pathology in neurons that contain TH and synthesize dopamine, noradrenaline or adrenaline. [source] Normal nigrostriatal innervation but dopamine dysfunction in mice carrying hypomorphic tyrosine hydroxylase allelesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Susanna Althini Abstract We investigated the use of the mouse tyrosine hydroxylase (TH) gene to drive knock-in constructs in catecholaminergic neurons. Two targeting constructs representing truncated forms of either of the BMP receptors ALK-2 or BMPR-II preceded by an internal ribosome entry site (IRES) were introduced into the 3, untranslated region of TH. An frt-flanked neomycin-resistance (neor) cassette was placed in the 3, end of the targeting constructs. Mice homozygous for the knock-in alleles showed various degrees of hypokinetic behavior, depending mainly on whether the neor cassette was removed. In situ hybridization and immunohistochemistry showed that TH mRNA and protein were variously down-regulated in these mouse strains. Reduced levels of dopamine and noradrenalin were found in several brain areas. However, number and morphology of neurons in substantia nigra and their projections to striatum appeared normal in the neor -positive TH hypomorphic mice as examined by markers for L-aromatic amino acid decarboxylase and the dopamine transporter. Elimination of the neor cassette from the knock-in alleles partially restored TH and dopamine levels. The present neor -positive TH hypomorphic mice show that nigrostriatal innervation develops independently of TH and should find use as a model for conditions of reduced catecholamine synthesis, as seen in, for example, L-dihydroxyphenylalanine-responsive dystonia/infantile parkinsonism. © 2003 Wiley-Liss, Inc. [source] The Absence of Phosphorylated Tyrosine Hydroxylase Expression in the Purkinje Cells of the Ataxic Mutant Pogo MouseANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2006N. S. Lee Summary The pogo mouse is a new ataxic autosomal recessive mutant that arose in Korean wild mice (KJR/Mskist). Its ataxic phenotype includes difficulty in maintaining a normal posture and the inability to walk in a straight line. Several studies have reported that tyrosine hydroxylase (TH) is persistently ectopically expressed in particular subsets of Purkinje cells in a parasagittal banding pattern in several ataxic mutant mice, e.g. tottering alleles and pogo mice. In this present study, we examined the expression of an enzymatically active form of TH and phosphorylated TH at Ser40 (phospho-TH) by using immunohistochemistry and double immunofluorescence in the cerebellum of pogo mice. TH immunostaining appeared in some Purkinje cells in pogo, but in only a few of Purkinje cells of their heterozygous littermate controls. In all groups of mice, no phospho-TH immunoreactive Purkinje cells were observed in the cerebellum, although subsets of TH immunoreactive Purkinje cells were found in adjacent sections. This study suggests that TH expression in the Purkinje cells of pogo abnormally increases without activation of this enzyme by phosphorylation. This may mean that TH in the Purkinje cells of these mutants does not catalyse the conversion of tyrosine to l -DOPA, and is not related to catecholamine synthesis. [source] Catecholamine synthesis and metabolism in the central nervous system of mice lacking ,2 -adrenoceptor subtypesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009MA Vieira-Coelho Background and purpose:, This study investigates the role of ,2 -adrenoceptor subtypes, ,2A, ,2B and ,2C, on catecholamine synthesis and catabolism in the central nervous system of mice. Experimental approach:, Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from ,2A -, ,2B - and ,2C -adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice. Key results:, Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in ,2A - and ,2C -adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in ,2A and ,2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; ,2AKO: 6.9 ± 0.7, 1.9 ± 0.1; ,2BKO: 2.3 ± 0.2, 1.0 ± 0.1; ,2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue),1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in ,2A and ,2CKO [WT: 40 ± 1; ,2A: 77 ± 2; ,2B: 40 ± 1; ,2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein),1·h,1], but no significant differences were found in dopamine ,-hydroxylase. Of the catabolic enzymes, catechol- O -methyltransferase enzyme activity was significantly higher in all three ,2KO mice [WT: 2.0 ± 0.0; ,2A: 2.4 ± 0.1; ,2B: 2.2 ± 0.0; ,2C: 2.2 ± 0.0 nmol·(mg protein),1·h,1], but no significant differences were found in monoamine oxidase activity between all ,2KOs and WT mice. Conclusions and implications:, In mouse brain, deletion of ,2A - or ,2C -adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any ,2 -adrenoceptor subtypes resulted in increased activity of catechol- O -methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in ,2A and ,2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. [source] | ||||||||||