Dopamine D2-like receptors and amino acid-induced glomerular hyperfiltration in humans.
OBJECTIVE
In rodents, blockade of dopamine D2-like receptors abolishes both the physiological increase in glomerular filtration rate (GFR) induced by amino acids and the pathological hyperfiltration in experimental diabetes mellitus. This study addressed the contribution of dopamine D2-like receptors to changes in renal haemodynamics after amino acid infusion in humans.


METHODS
Twelve healthy volunteers participated in this double-blind, randomized, cross-over study. GFR and renal blood flow (RPF) were assessed by renal clearance of inulin and p-aminohippuric acid (PAH), respectively. Following infusion of 0.45% saline at baseline, an electrolyte-balanced solution of mixed amino acids (10%) was infused. Prior to the experiments, the subjects received orally either placebo, or sulpiride (10 mg kg-1), a centrally and peripherally acting D2-like receptor antagonist, or domperidone (1 mg kg-1) which affects only peripheral D2-like receptors.


RESULTS
In the placebo series, amino acid infusion significantly increased GFR and RPF by up to 15.8 +/- 5.3% and 14.4 +/- 6.1%, respectively, while mean blood pressure and heart rate remained unchanged. Pretreatment with domperidone only marginally altered the renal response to amino acids (maximal increase by 13.2 +/- 5.6 and 11.9 +/- 4.0% in GFR and RPF, respectively), while sulpiride completely abolished the renal haemodynamic changes induced by amino acids. Total and fractional urinary sodium excretion as well as urinary osmolality were similar at baseline and increased in response to amino acids, to the same extent, in all series. No changes in renal dopamine excretion occurred.


CONCLUSIONS
The results indicate that in man dopamine D2-like receptors are involved in the renal haemodynamic response to amino acid infusion. Whether dopamine D2-like receptor blockade diminishes glomerular hyperfiltration in pathological states requires clinical investigations.
Luippold
G
G
Department of Pharmacology, University of Tübingen, Centre of Clinical Pharmacology Tübingen-Stuttgart, D-72074 Tübingen, Germany. gerd.luippold@uni-tuebingen.de
Schneider
S
S
Stefanescu
A
A
Benöhr
P
P
Mühlbauer
B
B
D000328:Adult; D000596:Amino Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004294:Domperidone / Q000493:pharmacokinetics / Q000494:pharmacology; D004298:Dopamine / Q000652:urine; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017595:Renal Plasma Flow / Q000187:drug effects; D013469:Sulpiride / Q000493:pharmacokinetics / Q000494:pharmacology
D000596:Amino Acids; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D004294:Domperidone; D013469:Sulpiride; D004298:Dopamine