| First Author | Moura E | Year | 2012 |
| Journal | Am J Physiol Renal Physiol | Volume | 303 |
| Issue | 7 | Pages | F928-38 |
| PubMed ID | 22859407 | Mgi Jnum | J:188615 |
| Mgi Id | MGI:5441166 | Doi | 10.1152/ajprenal.00217.2011 |
| Citation | Moura E, et al. (2012) alpha2C-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the mouse kidney. Am J Physiol Renal Physiol 303(7):F928-38 |
| abstractText | 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(2C)KO) 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 (IC(50): 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 muM), a MEK1/2 inhibitor. Kidney tissue levels of l-DOPA were significantly higher in alpha(2C)KO mice compared with wild-type mice (wild-type mice: 58 +/- 2 pmol/g tissue and alpha(2C)KO mice: 81 +/- 15 pmol/g tissue, P < 0.05) and in mice treated with JP-1302 (3 mumol/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. |
