L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-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 (K(m) 0.316 vs 1.53 microM). L-Dopa uptake was decreased by the nonselective adrenergic agonists epinephrine or norepinephrine (40%), by the beta-selective agonist isoproterenol or the beta(2)-selective agonist terbutaline (60%), but not by alpha-selective agonists (all 1 microM). The effect of norepinephrine, isoproterenol, or terbutaline was unaffected by addition of the beta(1)-antagonist atenolol, abolished by ICI-118, 551, a beta(2)-antagonist (both 0.1 microM), and mimicked by the addition of dibutyryl-cAMP (1 microM). Preincubation with terbutaline decreased the number of high-affinity uptake sites (V(max) = 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 microM). 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 beta(2)-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.