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Background and purpose: This study investigates the role of α2-adrenoceptor subtypes, α2A, α2B and α2C, 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 α2A-, α2B- and α2C-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 α2A- and α2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α2A and α2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α2CKO: 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 α2A and α2CKO [WT: 40 ± 1; α2A: 77 ± 2; α2B: 40 ± 1; α2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein)−1·h−1], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α2KO mice [WT: 2.0 ± 0.0; α2A: 2.4 ± 0.1; α2B: 2.2 ± 0.0; α2C: 2.2 ± 0.0 nmol·(mg protein)−1·h−1], but no significant differences were found in monoamine oxidase activity between all α2KOs and WT mice. Conclusions and implications: In mouse brain, deletion of α2A- or α2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α2-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α2A and α2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. |
