Dopamine D3 receptor activation modulates renal function in anesthetized rats.
The renal effects of the D3 receptor agonist R(+)-7-hydroxy-dipropyl-aminotetraline (7-OH-DPAT) were studied in anesthetized Sprague-Dawley rats using standard clearance experiments. 7-OH-DPAT infusion (0.01, 0.1, and 1.0 microg kg(-1) min(-1)) dose-dependently increased glomerular filtration rate (GFR) compared to baseline by a maximum of 20+/-2% while arterial blood pressure was not affected. Heart rate was not altered during the two lower doses of 7-OH-DPAT whereas a slight reduction occurred due to infusion of 1.0 microg kg(-1) min(-1). In contrast, higher doses of 7-OH-DPAT, starting from 3 microg kg(-1) min(-1), markedly influenced systemic hemodynamics. In addition to the hyperfiltration, 7-OH-DPAT (1.0 microg kg(-1) min(-1)) also induced a significant diuresis (27.7+/-4.3 microl min(-1) 100 g(-1) vs 16.2+/-5.4 microl min(-1) 100 g(-1)) and increased both absolute (3.30+/-0.58 micromol min(-1) 100 g(-1) vs 0.95+/-0.26 micromol min(-1) 100 g(-1)) and fractional sodium excretion (2.48+/-0.32% vs 0.79+/-0.19%). These changes in renal function were not modulated by pretreatment with the D2 receptor antagonist S(-)-sulpiride but abolished by the D3 antagonist 5,6-dimethoxy-2-(di-n-propylamino)indane (U-99194A). In coincidence with the action of 7-OH-DPAT on both glomerular and tubular function, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of D3 receptors in both glomerular and tubular fractions of kidneys taken from Sprague-Dawley rats. These data indicate that D3 receptors in the kidney are involved in the regulation of renal hemodynamics and tubular function.
Luippold
G
G
Department of Pharmacology, University of Tübingen, Germany.
Küster
E
E
Joos
T O
TO
Mühlbauer
B
B
D000758:Anesthesia; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin