Catecholamine synthesis and metabolism in the central nervous system of mice lacking α2-adrenoceptor subtypes

作者: MA Vieira‐Coelho , MP Serrao , J Afonso , CE Pinto , E Moura

DOI: 10.1111/J.1476-5381.2009.00375.X

关键词: CatabolismAromatic L-amino acid decarboxylaseNeurotransmitterMonoamine oxidaseEndocrinologyBiologyTyrosine hydroxylaseDopamineNorepinephrineInternal medicineCatecholamine

摘要: Background and purpose:  This study investigates the role of α2-adrenoceptor subtypes, α2A, α2B α2C, on catecholamine synthesis catabolism in central nervous system mice. Experimental approach:  Activities main synthetic catabolic enzymes were determined whole brains obtained from α2A-, α2B- α2C-adrenoceptor knockout (KO) C56Bl\7 wild-type (WT) mice. Key results:  Although no significant differences found tyrosine hydroxylase activity expression, brain tissue levels 3,4-dihydroxyphenylalanine threefold higher α2A- KO mice. Brain dopamine noradrenaline significantly α2A α2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 0.1; α2AKO: 6.9 0.7, 1.9 α2BKO: 2.3 0.2, 1.0 α2CKO: 4.6 0.8, 1.5 0.2 nmol·(g tissue)−1, for respectively]. Aromatic L-amino acid decarboxylase was α2CKO 40 1; α2A: 77 2; α2B: α2C: 50 1, maximum velocity (Vmax) nmol·(mg protein)−1·h−1], but β-hydroxylase. Of enzymes, catechol-O-methyltransferase enzyme all three α2KO mice 2.0 0.0; 2.4 2.2 0.0 monoamine oxidase between α2KOs mice. Conclusions implications:  In mouse brain, deletion or α2C-adrenoceptors increased cerebral aromatic levels. Deletion any subtypes resulted catechol-O-methyltransferase. Higher could be explained by transport.

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