Locally formed dopamine modulates renal Na-P(i) co-transport through DA₁ and DA₂ receptors

The involvement of dopamine (DA) receptor subtypes in regulation of renal phosphate transport by DA, either exogenous or locally synthesized from L-dihydroxyphenylalanine (L-dopa) was evaluated in opossum kidney (OK) cells with proximal tubular phenotype. DA synthesis from L-dopa by OK cells was abolished by carbidopa and benserazide, two dissimilar inhibitors of aromatic L-amino acid decarboxylase. L-Dopa stimulated cyclic AMP generation and inhibited Na-dependent P(i) uptake, and these effects were abolished by carbidopa and benserazide. The effects of L-dopa or DA on cyclic AMP generation and on Na-P(i) co-transport were mimicked by SKF 38393, a DA₁ receptor agonist, and were potentiated by S-sulpiride, a DA₂ receptor antagonist. Bromocriptine, a DA₂ receptor agonist, blunted in a pertussis toxin-dependent manner parathyroid hormone (PTH)-induced cyclic AMP generation and inhibition of P(i) uptake. In contrast with PTH, neither L-dopa nor DA affected significantly the cytosolic calcium concentration. These results support the involvement of DA₁ and DA₂ receptors, positively and negatively coupled into adenylate cyclase respectively, in modulation of renal phosphate transport.