Locally formed 5-hydroxytryptamine stimulates phosphate transport in cultured opossum kidney cells and in rat kidney.
Renal proximal tubular cells have been shown to express aromatic L-amino acid decarboxylase (L-AAAD), which converts L-dopa into dopamine and 5-hydroxytryptophan [(OH)Trp] into 5-hydroxytryptamine (5-HT; serotonin). Because 5-HT receptors have been demonstrated in proximal cells, we hypothesized that 5-HT may act as an autocrine/paracrine modulator of proximal transport. We evaluated this possibility in opossum kidney (OK) cells, a renal epithelial cell line with a proximal phenotype expressing 5-HT1B receptors, and in intact anaesthetized rats. 5-HT synthesis by OK cells increased with incubation time and (OH)Trp concentration, and was abolished by benserazide, an L-AAAD inhibitor. 5-HT reversed parathyroid hormone (PTH)-induced cAMP accumulation in a pertussis toxin-sensitive manner and reduced the PTH inhibition of P(i) uptake without affecting the NaP(i)-4 mRNA level. The effects of 5-HT on cAMP generation and Na-P(i) co-transport were reproduced by (OH)Trp, except in the presence of benserazide, and by L-propranolol and dihydroergotamine, two 5-HT1B receptor agonists. In rats, (OH)Trp and dihydroergotamine decreased fractional P(i) excretion. Benserazide abolished the effect of (OH)Trp but not that of dihydroergotamine.


CONCLUSIONS
(i) locally generated 5-HT blunts the inhibitory effect of PTH on Na-P(i) co-transport in OK cells; (ii) endogenous 5-HT decreases P(i) excretion in rats; and (iii) 5-HT is a paracrine modulator involved in the physiological regulation of renal P(i) transport.
Hafdi
Z
Z
Department of Physiology, Faculte de Medecine Xavier-Bichat, Université Paris 7, France.
Couette
S
S
Comoy
E
E
Prie
D
D
Amiel
C
C
Friedlander
G
G
D006916:5-Hydroxytryptophan / Q000378:metabolism / Q000494:pharmacology; D000409:Alanine / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001545:Benserazide / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004087:Dihydroergotamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004848:Epithelium; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology; D037342:Pertussis Toxin; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002352:Carrier Proteins; D008757:Methylglucosides; D010281:Parathyroid Hormone; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D004087:Dihydroergotamine; C027020:methylglucoside; D001545:Benserazide; D006916:5-Hydroxytryptophan; D000242:Cyclic AMP; D037342:Pertussis Toxin; D001142:Aromatic-L-Amino-Acid Decarboxylases; D000409:Alanine; D004298:Dopamine