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 o ppossum (OK) cells. We thus investigated the effects of 5-HT upon the Na+-Pi cotransport in cultured OK cells and its interactions with dopa mine. Incubation of OK cells with 1 nM-10 mu M 5-HT resulted in dose-d ependent stimulation of Na+-Pi cotransport (ED50 congruent to 8 nM) an d also counteracted inhibition of Na+-Pi cotransport elicited by dopam ine. 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 o f Na+-Pi cotransport. Incubation of OK cells with the 5-HT precursor 5 -hydroxytryptophan resulted in time- and dose-dependent accumulation o f 5-HT in the medium that also elicited an increase in Na+-Pi cotransp ort. Both the effects of 5-HT and dopamine on Na+-Pi cotransport were prevented by carbidopa. The stimulatory effect of 5-HT was specific fo r 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 p ropose that 5-HT and dopamine have opposite actions as paracrine/autoc rine regulators of Na+-Pi cotransport via opposite effects upon cAMP f ormation.