L-Dopa uptake and dopamine production in proximal tubular cells are regulated by b2-adrenergic receptors

Carranza, Andrea, Susana Nowicki, Marta Barontini, and Ines Armando. L-Dopa uptake and dopamine production in proximal tubular cells are regulated by b2adrenergic receptors. Am J Physiol Renal Physiol 279: F77–F83, 2000.—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 (Km 0.316 vs 1.53 mM). L-Dopa uptake was decreased by the nonselective adrenergic agonists epinephrine or norepinephrine (40%), by the b-selective agonist isoproterenol or the b2-selective agonist terbutaline (60%), but not by a-selective agonists (all 1 mM). The effect of norepinephrine, isoproterenol, or terbutaline was unaffected by addition of the b1-antagonist atenolol, abolished by ICI-118,551, a b2-antagonist (both 0.1 mM), and mimicked by the addition of dibutyryl-cAMP (1 mM). Preincubation with terbutaline decreased the number of high-affinity uptake sites (Vmax 5 1.10 6 0.3 vs. 0.5 6 0.1 pmol z mg protein z min) without changing their affinity. Norepinephrine or terbutaline decreased dopamine production by isolated cells, and this effect was abolished by ICI-118,551 (0.1 mM). 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 b2-adrenergic receptors decreases the number of high-affinity Ldopa 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.