title: Dopamine-1 receptors in rat proximal convoluted tubule: regulation by intrarenal dopamine.
abstract: Dopamine (DA) is synthesized in the renal proximal convoluted tubule (PCT) and may act as a paracrine substance at tubular DA-1 receptors to decrease sodium transport. Although DA-1 receptors have been identified in rabbit renal PCT by use of nonselective dopaminergic radioligands, DA-1 receptors have not been localized in specific nephron segments with the use of selective DA-1 radioligands. In these studies we used a novel DA-1 dopaminergic ligand 125I-SCH-23982, which has been shown to have a high affinity for brain and renal DA-1 receptors, to identify DA-1 receptors in the rat renal PCT and distal convoluted tubule (DCT). DA-1 receptors in the microdissected PCT and DCT were studied by a quantitative autoradiographic technique and by measuring adenylate cyclase (AC) activity. No specific 125I-SCH-23982 binding could be measured in the DCT indicating the absence of DA-1 receptors in this segment. Binding of 125I-SCH-23982 to PCT was saturable with time and radioligand concentration and was stereoselective. Saturation isotherm analysis in control rats yielded a dissociation constant (Kd) of 7.5 +/- 0.14 nM (n = 4) and a maximum receptor density (Bmax) of 0.69 +/- 0.04 pmol/mg protein (n = 4). The rank-order potency for agonist and antagonist displacement of 125I-SCH-23982 binding was consistent for DA-1 receptors: SCH-23390 greater than fenoldopam = SKF 38393 greater than SCH-23388. The stimulatory effect of the DA-1 agonist fenoldopam (10 microM) on AC activity was blocked by the DA-1 antagonist SCH-23390 (10 microM) but not by the beta-adrenergic antagonist (-)-propranolol (10 microM), indicating specificity. The DA-beta-hydroxylase blocker, SKF 102698, increased renal DA concentrations threefold, reduced the PCT DA-1 receptor Bmax by 33%, and abolished the stimulatory effect of 10 microM fenoldopam on AC activity in the PCT but had no effect on Kd. It is concluded that DA-1 receptors are present in rat PCT but not DCT and can be regulated by renal DA.
authors: Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume City, Japan.
authors: S
authors: S
authors: Kinoshita
authors: E H
authors: EH
authors: Ohlstein
authors: R A
authors: RA
authors: Felder
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1
chemical_list: C052414:1-(3,5-difluorobenzyl)imidazole-2-thiol; D007093:Imidazoles; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D004299:Dopamine beta-Hydroxylase; D000262:Adenylyl Cyclases; D004298:Dopamine