alpha(2C)-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the mouse kidney

• Type: Article in International Scientific Journal
• Date: 2012

Authors

moura, e (Author) Other; silva, e (Author) Other; serrao, mp (Author) Other; afonso, j (Author) Other; kozmus, cep (Author) Other; vieira-coelho, ma (Author) FMUP

Journal

The Journal is awaiting validation by the Administrative Services.

Title: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY

Vol. 303

Pages: F928-F938

ISSN: 1931-857X

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-4Z8

DOI: 10.1152/ajprenal.00217.2011

Abstract (EN): Moura E, Silva E, Serrao MP, Afonso J, Kozmus CE, Vieira-Coelho MA. alpha(2C)-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the mouse kidney. Am J Physiol Renal Physiol 303: F928- F938, 2012. First published August 1, 2012; doi:10.1152/ajprenal.00217.2011.-Targeted deletion or selective pharmacological inhibition of alpha(2C)-adrenoceptors in mice results in increased brain tissue levels of dopamine and its precursor L-3,4-dihydroxyphenylalanine (L-DOPA), without significant changes in L-DOPA synthesis. L-DOPA uptake is considered the rate-limiting step in dopamine synthesis in the kidney. Since alpha(2C)-adrenoceptors may influence the transport of L-DOPA, we investigated the effect of alpha(2C)-adrenoceptor activation on L-DOPA uptake in a kidney cell line (opossum kidney cells). L-DOPA and dopamine kidney tissue levels in alpha(2C)-adrenoceptor knockout (alpha 2CKO) mice and in mice treated with the selective alpha(2C)-adrenoceptor antagonist JP-1302 were also evaluated. The alpha(2)-adrenoceptor agonist medetomidine (0.1-1,000 nM) produced a concentration-dependent decrease in L-DOPA uptake in opossum kidney cells (IC50: 2.5 +/- 0.5 nM and maximal effect: 28 +/- 5% of inhibition). This effect was abolished by a preincubation with JP-1302 (300 nM). Furthermore, the effect of medetomidine (100 nM) was abolished by a preincubation with U-0126 (10 mu M), a MEK1/2 inhibitor. Kidney tissue levels of L-DOPA were significantly higher in alpha 2CKO mice compared with wild-type mice (wild-type mice: 58 +/- 2 pmol/g tissue and alpha 2CKO mice: 81 +/- 15 pmol/g tissue, P < 0.05) and in mice treated with JP-1302 (3 mu mol/kg body wt) compared with control mice (control mice: 62 +/- 2 pmol/g tissue and JP-1302-treated mice: 75 +/- 1 pmol/g tissue, P < 0.05), both without significant changes in dopamine kidney tissue levels. However, mice treated with JP-1302 on a high-salt diet presented significantly higher dopamine levels in the kidney and urine compared with control animals on a high-salt diet. In conclusion, in a kidney cell line, alpha(2C)-adrenoceptor activation inhibits L-DOPA uptake, and in mice, deletion or blockade of alpha(2C)-adrenoceptors increases L-DOPA kidney tissue levels.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11