Catecholamine synthesis and metabolism in the central nervous system of mice lacking alpha(2)-adrenoceptor subtypes

• Type: Article in International Scientific Journal
• Date: 2009

Authors

vieira-coelho, ma (Author) FMUP; serrao, mp (Author) Other; afonso, j (Author) Other; pinto, ce (Author) Other; moura, e (Author) Other

Journal

Title: British Journal of Pharmacology

Vol. 158

Pages: 726-737

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-F62

DOI: 10.1111/j.1476-5381.2009.00375.x

Abstract (EN): Background and purpose: This study investigates the role of alpha(2)-adrenoceptor subtypes, alpha(2A), alpha(2B) and alpha(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 alpha(2A)-, alpha(2B)- and alpha(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 alpha(2A)- and alpha(2C)-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in alpha(2A) and alpha 2CKOs compared with WT [WT: 2.8 +/- 0.5, 1.1 +/- 0.1; alpha 2AKO: 6.9 +/- 0.7, 1.9 +/- 0.1; alpha 2BKO: 2.3 +/- 0.2, 1.0 +/- 0.1; alpha 2CKO: 4.6 +/- 0.8, 1.5 +/- 0.2 nmol center dot(g tissue)-1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in alpha(2A) and alpha 2CKO [WT: 40 +/- 1; alpha(2A): 77 +/- 2; alpha(2B): 40 +/- 1; alpha(2C): 50 +/- 1, maximum velocity (V-max) in nmol center dot(mg protein)-1 center dot h-1], but no significant differences were found in dopamine beta-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three alpha 2KO mice [WT: 2.0 +/- 0.0; alpha(2A): 2.4 +/- 0.1; alpha(2B): 2.2 +/- 0.0; alpha(2C): 2.2 +/- 0.0 nmol center dot(mg protein)-1 center dot h-1], but no significant differences were found in monoamine oxidase activity between all alpha 2KOs and WT mice. Conclusions and implications: In mouse brain, deletion of alpha(2A)- or alpha(2C)-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any alpha(2)-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in alpha(2A) and alpha 2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12