Title

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

Document Type

Journal Article

Publication Date

1-1-2000

Journal

American Journal of Physiology - Renal Physiology

Volume

279

Issue

1 48-1

DOI

10.1152/ajprenal.2000.279.1.f77

Keywords

Catecholamines; Cellular transport; Kidney; L-3,4-dihydroxyphenylalanine

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 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 (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 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.

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