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Dopamine is metabolised by different enzymes along the rat nephron

  • Renal Function, Body Fluids
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Abstract

The purpose of this study was to determine the basal levels of dopamine (DA) and to examine the enzymes involved in DA metabolism in different microdissected nephron segments from rat kidneys. Segments were incubated with DA (50 nM) or DA plus monoamine oxidase (MAO) or catechol-O-methyl transferase (COMT) inhibitors. Basal DA levels were higher in the proximal convoluted tubule (PCT, 10.8±3.7 pg/mm) and in the medullary collecting duct (MCD, 10.9±4.0 pg/mm) than in the medullary thick ascending limb of Henle’s loop (MTAL, 4.9±0.9 pg/mm) (P<0.05). The percentage of exogenously added DA that was not metabolised was similar in both PCT (67±13%) and MCD (65±5%) and lower in MTAL (35±7%), suggesting that MTAL is a major site of DA metabolism. Inhibition of MAO (pargyline 1 mM) significantly increased the basal content of DA and the percentage of the added non-metabolised DA (to 95±10%) in PCT but had no effect on MTAL or MCD. Conversely, inhibition of COMT (nitecapone or Ro-41-0960, both 1 mM) slightly increased the basal levels of DA only in MTAL, whereas the percentage of added DA not metabolised rose to 97±10% in MTAL and to 91±15% in MCD. COMT inhibition had no effect in PCT. In conscious rats pargyline (50 mg/kg) increased urinary DA from 680±34 to 1,128±158 ng/d/100 g BW (P<0.01) while nitecapone (40 mg/kg) produced a slight non-significant increment. Our results show that DA is present all along the rat nephron and that renal DA is metabolised continuously and predominantly by MAO in proximal segments, and by COMT in the more distal ones.

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Acknowledgements

The present work was supported by a grant R. Carrillo, A. Oñativia 2001 of Ministerio de Salud, Argentina and by Agencia Nacional de Promoción Científica y Tecnológica, PICT 00-05-8658 and PIPs 573/98, 2867/01 and PEI 6477/03.

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Authors and Affiliations

  1. Laboratorio de Riñón Experimental, Instituto de Investigaciones Médicas A. Lanari, Combatientes de Malvinas, 3150 C1427ARO, Buenos Aires, Argentina

    Fernando R. Ibarra, Verónica De Luca Sarobe & Elvira E. Arrizurieta

  2. Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), Hospital de Niños R. Gutierrez, Gallo, 1360, C1425EFD, Buenos Aires, Argentina

    Inés Armando, Susana Nowicki, Andrea Carranza & Marta Barontini

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  1. Fernando R. Ibarra
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  2. Inés Armando
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  3. Susana Nowicki
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  4. Andrea Carranza
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  5. Verónica De Luca Sarobe
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  6. Elvira E. Arrizurieta
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  7. Marta Barontini
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Correspondence to Fernando R. Ibarra.

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Ibarra, F.R., Armando, I., Nowicki, S. et al. Dopamine is metabolised by different enzymes along the rat nephron. Pflugers Arch - Eur J Physiol 450, 185–191 (2005). https://doi.org/10.1007/s00424-005-1386-6

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  • DOI: https://doi.org/10.1007/s00424-005-1386-6

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