title: Increased renal dopamine and acute renal adaptation to a high-phosphate diet.
abstract: The current experiments explore the role of dopamine in facilitating the acute increase in renal phosphate excretion in response to a high-phosphate diet. Compared with a low-phosphate (0.1%) diet for 24 h, mice fed a high-phosphate (1.2%) diet had significantly higher rates of phosphate excretion in the urine associated with a two- to threefold increase in the dopamine content of the kidney and in the urinary excretion of dopamine. Animals fed a high-phosphate diet had a significant increase in the abundance and activity of renal DOPA (l-dihydroxyphenylalanine) decarboxylase and significant reductions in renalase, monoamine oxidase A, and monoamine oxidase B. The activity of protein kinase A and protein kinase C, markers of activation of renal dopamine receptors, were significantly higher in animals fed a high-phosphate vs. a low-phosphate diet. Treatment of rats with carbidopa, an inhibitor of DOPA decarboxylase, impaired adaptation to a high-phosphate diet. These experiments indicate that the rapid adaptation to a high-phosphate diet involves alterations in key enzymes involved in dopamine synthesis and degradation, resulting in increased renal dopamine content and activation of the signaling cascade used by dopamine to inhibit the renal tubular reabsorption of phosphate.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, 21201, USA. eweinman1440@yahoo.com
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinman
authors.forename: Rajatsubhra
authors.initials: R
authors.lastname: Biswas
authors.forename: Deborah
authors.initials: D
authors.lastname: Steplock
authors.forename: Peili
authors.initials: P
authors.lastname: Wang
authors.forename: Yuen-Sum
authors.initials: YS
authors.lastname: Lau
authors.forename: Gary V
authors.initials: GV
authors.lastname: Desir
authors.forename: Shirish
authors.initials: S
authors.lastname: Shenolikar
mesh_terms: D000222:Adaptation, Physiological; D000704:Analysis of Variance; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002230:Carbidopa / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D016226:Phosphorus, Dietary; D008995:Monoamine Oxidase; C521557:renalase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D004296:Dopa Decarboxylase; D002230:Carbidopa; D004298:Dopamine