Autocrine/paracrine regulation of renal Na(+)-phosphate cotransport by dopamine.
We tested the hypothesis that dopamine (DA) acts as an autocrine/paracrine regulator of Na(+)-Pi symport in proximal tubules, using opossum kidney (OK) cells as an in vivo model. Both DA and parathyroid hormone (PTH) increased adenosine 3',5'-cyclic monophosphate (cAMP) and inhibited Na(+)-gradient-dependent uptake of 32P but not that of L-[3H]-alanine. Incubation of OK cells with L-dopa, a DA precursor, resulted in accumulation of DA (7.4 nM), a ninefold increase of cAMP in the medium, and an inhibition (-10%) of Na(+)-Pi uptake. Carbidopa, an inhibitor of aromatic-L-amino acid decarboxylase, prevented the formation of DA from L-dopa, the increase in cAMP, and the inhibition of Na(+)-Pi cotransport. Pi-replete OK cells produced more DA (+15%) from L-dopa than Pi-deprived cells; however, the endogenous DA inhibited Na(+)-Pi cotransport both in Pi-deprived and in Pi-replete cells. Thus OK cells can synthesize DA from L-dopa in a quantity sufficient to elicit both the maximum DA-stimulated cAMP accumulation and inhibition of Na(+)-Pi cotransport in the same cell population. Our data, obtained on an in vitro system, support the hypothesis proposing that DA generated in proximal tubular cells can modulate, via cAMP, the Na(+)-Pi symport in the same or adjacent cells. If present in the kidney, this pathway might represent an autocrine/paracrine system that can contribute to regulation of renal Pi homeostasis.
Department of Medicine, Mayo Clinic and Foundation, Mayo Medical School, Rochester, Minnesota 55905.
R P
RP
Glahn
M J
MJ
Onsgard
G M
GM
Tyce
S L
SL
Chinnow
F G
FG
Knox
T P
TP
Dousa
D000409:Alanine / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002230:Carbidopa / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D006706:Homeostasis / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009893:Opossums / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010761:Phosphorus Radioisotopes / Q000493:pharmacokinetics; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D010761:Phosphorus Radioisotopes; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D000242:Cyclic AMP; D002230:Carbidopa; D000409:Alanine; D004298:Dopamine