L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-adrenergic receptors.
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.
Carranza
A
A
Centro de Investigaciones Endocrinológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, 1425 Buenos Aires, Argentina.
Nowicki
S
S
Barontini
M
M
Armando
I
I
D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007980:Levodopa / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000652:urine; D011412:Propanolamines / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; C026777:ICI 118551; D003994:Bucladesine; D007545:Isoproterenol; D013726:Terbutaline; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine