AJP - Renal Physiology, Vol 259, Issue 2 297-F303, Copyright © 1990 by American Physiological Society
Dopamine inhibits Na(+)-H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase
C. C. Felder, T. Campbell, F. Albrecht and P. A. Jose
Section of Pharmacology, National Institute of Mental Health, Bethesda, Maryland 20892.
To determine a renal tubular mechanism for the natriuretic effect of
dopamine (DA) and DA-1 agonists, we measured Na(+)-H+ exchange activity
(amiloride sensitive) in rat renal cortical brush-border membrane vesicles
(BBMV). Renal cortical tissues were preincubated with ligands before BBMV
preparation to study Na(+)-H+ exchange activity in the absence of the added
ligands that may compete for ion binding sites of the exchanger. DA and
DA-1 agonist-inhibited Na(+)-H+ exchange activity was concentration and
time dependent. The inhibitory effect was not due to increased
permeability, collapse of the proton gradient, or change in vesicle size
and did not extend to Na(+)-glucose symport. DA-2 agonists had no effect,
whereas alpha-adrenergic agonists increased Na(+)-H+ exchange activity.
Kinetic analysis revealed that the DA-1 agonist inhibited Na(+)-H+ exchange
activity by a noncompetitive process. 2',5'-Dideoxyadenosine inhibited
adenylate cyclase activity and reversed the inhibitory effect of DA-1
agonist on the exchanger. H4, an isoquinoline sulfonamide, which inhibits
protein kinase A, also reversed the inhibitory effect of DA-1 agonist on
the exchanger. Thus the DA-1 agonist-mediated inhibition of Na(+)-H+
exchange activity in BBMV is a receptor-mediated adenylate cyclase-linked
process.
