Dopamine regulates phosphate uptake by opossum kidney cells through multiple counter-regulatory receptors

The purpose of this study was to determine the mechanisms of dopamine regulation of phosphate uptake in opossum kidney (OK) cells, a model of proximal renal tubules. Dopamine stimulated cAMP generation and inhibited radiolabeled phosphate uptake into OK cell monolayers by 14.4 ± 1.8%. The effect of dopamine was transient, as phosphate uptake returned toward control level by 3 h despite the continued presence of dopamine. Pretreatment with pertussis toxin increased dopamine inhibition of phosphate uptake to 25 ± 3%, increased the duration of the doparnine effect to at least 3 h, and enhanced cAMP generation. In an OK cell clone that overexpressed cAMP phosphodiesterase, dopamine did not inhibit phosphate uptake, but pharmacologic inhibition of protein kinase A activation did not prevent dopamine inhibition of phosphate uptake. A DA₁ receptor agonist inhibited phosphate uptake more potently than dopamine (29.5 ± 1.1%) or a DA₂ receptor agonist (7.9 ± 2%). However, both DA₁ and DA₂ receptor antagonists completely blocked dopamine inhibition of phosphate uptake. DA₁, but not the DA₂, antagonists blocked dopamine-stimulated cAMP generation. Treatment with α-adrenergic receptor antagonists potentiated dopamine inhibition of phosphate uptake to the same extent as pertussis toxin and was not additive with pertussis toxin. It is concluded that dopamine inhibits phosphate uptake through DA₁ and DA₂ receptor stimulation by cAMP-dependent and -independent pathways and activates a pertussis toxin-sensitive counter- regulatory pathway that attenuates this response through α-adrenergic receptor stimulation.