title: Dopamine inhibits renal Na+:HCO3- cotransporter in rabbits and normotensive rats but not in spontaneously hypertensive rats.
abstract: BACKGROUND
  Dopamine (DA) is thought to regulate renal proximal transport through the inhibition of the Na+,K+-ATPase and/or Na+/H+ exchanger. Defects in this dopaminergic system are proposed to be a pathogenic factor of genetic hypertension. However, microperfusion studies have not consistently confirmed direct tubular effects of DA.
  
  
  METHODS
  Isolated proximal straight tubules were perfused peritubularly with Dulbecco's modified Eagle's tissue culture medium (DMEM) containing norepinephrine (NE) to improve incubation conditions. Intracellular Na+ concentrations ([Na+]i) and cell pH (pHi) were measured with fluorescence probes.
  
  
  RESULTS
  When incubated in DMEM plus NE, DA increased [Na+]i in rabbit tubules. Inhibition of Na+,K+-ATPase could not explain this response, as it was not suppressed by ouabain. An analysis of pHi responses to bath HCO3- reduction revealed that DA, SKF 38393 (a DA1 agonist), and adenosine 3',5'-cyclic monophosphate (cAMP) inhibited the basolateral Na+:HCO3- cotransporter in rabbit and Wistar-Kyoto rat (WKY), if its transport stoichiometry was converted to 3 HCO3-:1 Na+ by DMEM plus NE incubation. The inhibitory effect of DA was abolished by SCH 23390, a DA1 antagonist, but not by (-)-sulpiride, a DA2 antagonist. In spontaneously hypertensive rats (SHRs), however, DA and SKF 38393 failed to inhibit the cotransporter, although the inhibitory effects of cAMP and parathyroid hormone were comparable to those in WKY.
  
  
  CONCLUSIONS
  These results indicate that DA inhibits the Na+:HCO3- cotransporter in renal proximal tubules and also suggest that dysregulation of the cotransporter, possibly through the defect in DA1 receptor signaling, could play an important role in development of hypertension in SHRs.
authors.affiliation: Department of Nephrology and Endocrinology, and Department of Infectious Diseases, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kunimi
authors.forename: G
authors.initials: G
authors.lastname: Seki
authors.forename: C
authors.initials: C
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Uwatoko
authors.forename: A
authors.initials: A
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Fujita
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D006977:Hypertension, Renal / Q000235:genetics / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D012964:Sodium / Q000493:pharmacokinetics; D027982:Sodium-Bicarbonate Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D002352:Carrier Proteins; D004232:Diuretics; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D017447:Receptors, Dopamine D1; D027982:Sodium-Bicarbonate Symporters; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D012964:Sodium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D000086:Acetazolamide; D004298:Dopamine