Opposite paracrine effects of 5-HT and dopamine on Na(+)-Pi cotransport in opossum kidney cells.
Serotonin (5-HT) was recently reported to inhibit cAMP generation in oppossum (OK) cells. We thus investigated the effects of 5-HT upon the Na(+)-Pi cotransport in cultured OK cells and its interactions with dopamine. Incubation of OK cells with 1 nM-10 microM 5-HT resulted in dose-dependent stimulation of Na(+)-Pi contransport (ED50 approximately equal to 8 nM) and also counteracted inhibition of Na(+)-Pi cotransport elicited by dopamine. Pre-incubation with 5-HT decreased cAMP accumulation elicited by forskolin or dopamine and pre-treatment with pertussis toxin abolished both the inhibitory effect of 5-HT upon cAMP levels and stimulation of Na(+)-Pi cotransport. Incubation of OK cells with the 5-HT precursor 5-hydroxytryptophan resulted in time- and dose-dependent accumulation of 5-HT in the medium that also elicited an increase in Na(+)-Pi cotransport. Both the effects of 5-HT and dopamine on Na(+)-Pi cotransport were prevented by carbidopa. The stimulatory effect of 5-HT was specific for the Na(+)-Pi cotransport system since no effects were observed on Na(+)-alanine cotransport. The results indicate that 5-HT stimulates Na(+)-Pi cotransport at least in part via inhibition of cAMP accumulation. We propose that 5-HT and dopamine have opposite actions as paracrine/autocrine regulators of Na(+)-Pi cotransport via opposite effects upon cAMP formation.
de Toledo
F G
FG
Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
Beers
K W
KW
Berndt
T J
TJ
Thompson
M A
MA
Tyce
G M
GM
Knox
F G
FG
Dousa
T P
TP
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008962:Models, Theoretical; D009893:Opossums; D037342:Pertussis Toxin; D012701:Serotonin / Q000096:biosynthesis / Q000494:pharmacology*; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010566:Virulence Factors, Bordetella; C052168:sodium-alanine cotransporter; D012701:Serotonin; D006916:5-Hydroxytryptophan; D000242:Cyclic AMP; D037342:Pertussis Toxin; D004298:Dopamine