Dopamine-1 receptors in rat proximal convoluted tubule: regulation by intrarenal dopamine
| Autor: | E. H. Ohlstein, S. Kinoshita, R. A. Felder |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Physiology Dopamine Dopamine beta-Hydroxylase Nephron Kidney Binding Competitive Rats Inbred WKY Receptors Dopamine Kidney Tubules Proximal Radioligand Assay Internal medicine medicine Animals heterocyclic compounds Distal convoluted tubule Kidney Tubules Distal Receptor Chemistry Receptors Dopamine D1 Dopaminergic Imidazoles Rats medicine.anatomical_structure Convoluted tubule Endocrinology Dopamine receptor Adenylyl Cyclases medicine.drug |
| Zdroj: | American Journal of Physiology-Renal Physiology. 258:F1068-F1074 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.1990.258.4.f1068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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