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 mu M 5-HT resulted in dose-dependent stimulation of Na+-Pi cotransport (ED50 congruent 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.