The significance of L-amino acid decarboxylase and DARPP-32 in the kidney.
This study examines the role of endogenous dopamine (DA) for the regulation of renal tubular sodium (Na) transport. The enzyme L-amino acid decarboxylase (L-AADC) that converts L-dopa to DA has been localized to the proximal tubule cells with immunocytochemistry. Locally formed DA will inhibit the activity of Na-K-ATPase, the enzyme that yields energy to active Na transport. The effect is of physiological importance during high salt diet. The phosphoprotein DARPP-32, a DA1 receptor associated third messenger is abundant in the medullary thick ascending limb of Henle (mTAL). DARPP-32 is phosphorylated after activation of DA1 receptors. DARPP-32 is in its phosphorylated form a potent phosphatase inhibitor. Activation of the DA1 receptor in mTAL with the DA1 agonist SKF 82526 causes dose-dependent inhibition of Na-K-ATPase activity. The effect involves activation of cAMP protein kinase. It is likely that this effect is potentiated by DARPP-32.
Aperia
A
A
Department of Pediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
Hökfelt
T
T
Meister
B
B
Bertorello
A
A
Fryckstedt
J
J
Holtbäck
U
U
Seri
I
I
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology; D008138:Loop of Henle / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D011954:Receptors, Dopamine / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011954:Receptors, Dopamine; D007980:Levodopa; D012964:Sodium; D001142:Aromatic-L-Amino-Acid Decarboxylases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine