l-Dopa uptake and dopamine production in proximal tubular cells are regulated by β2-adrenergic receptors

Abstract

This study assessed the role of adrenergic receptors on the regulation of the uptake of l-dopa and the production of dopamine by renal tubular cells. Scatchard analysis showed two l-dopa uptake sites with different affinities ( Km0.316 vs 1.53 μM). l-Dopa uptake was decreased by the nonselective adrenergic agonists epinephrine or norepinephrine (40%), by the β-selective agonist isoproterenol or the β2-selective agonist terbutaline (60%), but not by α-selective agonists (all 1 μM). The effect of norepinephrine, isoproterenol, or terbutaline was unaffected by addition of the β1-antagonist atenolol, abolished by ICI-118,551, a β2-antagonist (both 0.1 μM), and mimicked by the addition of dibutyryl-cAMP (1 μM). Preincubation with terbutaline decreased the number of high-affinity uptake sites ( Vmax= 1.10 ± 0.3 vs. 0.5 ± 0.1 pmol · mg protein−1· min−1) without changing their affinity. Norepinephrine or terbutaline decreased dopamine production by isolated cells, and this effect was abolished by ICI-118,551 (0.1 μM). In vivo administration of ICI-118,551 reduced the urinary excretion of l-dopa and increased the excretion of 3,4-dihydroxyphenylacetic acid without significant changes in plasma l-dopa concentrations. These results demonstrate that stimulation of β2-adrenergic receptors decreases the number of high-affinity l-dopa uptake sites in isolated tubular cells resulting in a reduction of the uptake of l-dopa and the production of dopamine and provide evidence for the presence of this mechanism in the intact animal.