The signal transducer for the dopamine-1 regulated sodium transport in renal cortical brush border membrane vesicles.
We have reported the presence of dopamine-1 (DA-1) and dopamine-2 (DA-2) receptors in renal brush border and basolateral membranes. DA-1 agonists stimulate adenylate cyclase (AC) and phospholipase C (PLC) activity in both membranes. Moreover, the ability of a DA-1 agonist (fenoldopam) to stimulate PLC activity is independent of AC activity. A DA-2 agonist (LY171555) by itself was without effect and did not enhance the ability of the DA-1 agonist to stimulate PLC activity. The DA-1 but not DA-2 agonists inhibit Na+/H+ exchange activity in brush border membrane vesicles (BBMV) and Na+/K(+)-ATPase activity in basolateral membranes. However, cAMP inhibits, while protein kinase C (presumably via PLC activity) stimulates, Na+/H+ exchange activity. We therefore determined the effect of DA-1 agonists on Na+/H+ exchange activity when PLC or AC activity was blocked using neomycin or dideoxyadenosine, respectively. The drugs were incubated with minced renal cortex prior to preparation of BBMV by differential centrifugation and MnCl2 precipitation. Enrichment of BBMV was not affected by drug treatment. The Na+/H+ exchange activity was assessed by measuring amiloride (1 mmol/L) sensitive 22Na+ uptake in BBMV (pHi = 5.5, pHo = 7.5, Nai+ = O, Nao+ = 1 mmol/L). Neomycin inhibited DA and DA-1-stimulated PLC activity in BBMV in a concentration dependent manner (10(-6) to 10(-4) mol/L). Neomycin (10(-4) mol/L) completely blocked the ability of DA and DA-1 agonist to stimulate PLC activity but had no consistent effect on DA-1 inhibited Na+/H+ exchange activity. Dideoxyadenosine inhibited DA and DA-1 simulated AC activity without affecting DA-1 stimulated PLC activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Felder
C C
CC
Section on Pharmacology, National Institute of Mental Health, Bethesda, Maryland.
Albrecht
F
F
Eisner
G M
GM
Jose
P A
PA
D000818:Animals; D001692:Biological Transport; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004573:Electrolytes / Q000652:urine; D006801:Humans; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases / Q000378:metabolism
D015259:Dopamine Agents; D004573:Electrolytes; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D012964:Sodium; D011493:Protein Kinase C; D010738:Type C Phospholipases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine