Control of electrolyte transport in the kidney through a dopamine- and cAMP-regulated phosphoprotein, DARPP-32.
1. DARPP-32 is a phosphoprotein regulated by dopamine and cAMP. In its phosphorylated form it acts as an inhibitor of protein phosphatase-1, thereby regulating the phosphorylation state of phosphoproteins in the basal ganglia. 2. In the kidney, DARPP-32 has been detected in the medullary thick ascending limb of Henle (mTAL) and, to a lesser degree, in the proximal convoluted tubule by means of immunohistochemistry and in situ hybridization. 3. In single microdissected tubules of rat kidney, Na+, K(+)-ATPase activity, measured as ouabain-sensitive ATP hydrolysis, has been shown to be inhibited to the same degree by the DA1 agonist fenoldopam, cAMP and a synthesized and phosphorylated DARPP-32 peptide, D32(8-38). 4. It is concluded that the DA1 receptor-mediated inhibition of Na+ transport in the mTAL by dopamine occurs via cAMP accumulation and the phosphoprotein, DARPP-32.
Fryckstedt
J
J
Department of Paediatrics, St Gorans Hospital, Stockholm, Sweden.
Meister
B
B
Aperia
A
A
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004573:Electrolytes / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004573:Electrolytes; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine