Effects of costimulation of dopamine D1- and D2-like receptors on renal function.
In vitro studies have suggested that dopamine D1- and D2-like receptors interact to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist with the rank-order potency D3 >/= D4 > D2 > D5 > D1, to test the hypothesis that D1- and D2-like receptors interact to inhibit renal sodium transport in vivo in anesthetized rats. Increasing doses of Z-1046, administered via the right renal artery, increased renal blood flow (RBF), urine flow, and absolute and fractional sodium excretion without affecting glomerular filtration rate. For determination of the dopamine receptor involved in the renal functional effects of Z-1046, another group of rats received Z-1046 at 2 microgram . kg-1 . min-1 (n = 10) in the presence or absence of the D2-like receptor antagonist domperidone and/or the D1-like antagonist SCH-23390. Domperidone alone had no effect but blocked the Z-1046-mediated increase in urine flow and sodium excretion; it enhanced the increase in RBF after Z-1046. SCH-23390 by itself decreased urine flow and sodium excretion without affecting RBF and blocked the diuretic, natriuretic, and renal vasodilatory effect of Z-1046. We conclude that the renal vasodilatory effect of Z-1046 is D1-like receptor dependent, whereas the diuretic and natriuretic effects are both D1- and D2-like receptor dependent.
Department of Pediatrics, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
P A
PA
Jose
L D
LD
Asico
G M
GM
Eisner
F
F
Pocchiari
C
C
Semeraro
R A
RA
Felder
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009284:Naphthols / Q000008:administration & dosage / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000502:physiology
D001552:Benzazepines; D018491:Dopamine Agonists; D009284:Naphthols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C105333:Z1046; D004294:Domperidone