Absence of amino acid-induced glomerular hyperfiltration in dopamine D₃ receptor knockout mice

Abstract

Pharmacological inhibition of receptors of the dopamine D₂-like family has been shown to abolish the glomerular hyperfiltration in response to amino acids. To further discriminate between the receptor subtypes within the D₂-like family, we investigated the effects of amino acid infusion on renal function in dopamine D₃ receptor knockout (–/–) mice. In clearance experiments pentobarbital-anesthetized D₃ receptor (–/–) and wild-type (+/+) mice were infused with Ringer solution at baseline, followed by a continuous infusion of mixed amino acids (10%). Baseline glomerular filtration rate (GFR), assessed by renal clearance of [³H]-inulin, was the same in D₃ receptor (–/–) mice (0.56±0.08 ml/min per g kidney weight) and wild-type animals (0.56±0.04 ml/min per g kw). During infusion of amino acids, GFR was significantly elevated by 50% in D₃ receptor (+/+) mice. In contrast, this amino acid-induced response of GFR was abolished in D₃ receptor (–/–) mice. Baseline urinary water and sodium excretion was not significantly different in both groups of mice. As observed in GFR, these renal excretory parameters were significantly elevated during amino acid infusion in D₃ receptor (+/+) but not in D₃ receptor (–/–) mice. Time controls, constantly infused with Ringer solution, did not show significant changes in GFR, renal water or sodium excretion during the entire experiment, indicating stable experimental conditions. Taken together, the data underline the involvement of dopamine D₂-like receptors in the renal response to amino acid infusion and, in addition, attribute this effect to the dopamine D₃ receptor subtype.