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regulation of Na/H exchanger-3 activity in rat renal
proximal tubules during development
Departments of 1 Pediatrics, 2 Physiology and Biophysics, and 4 Medicine, Georgetown University Medical Center, Washington, District of Columbia 20007; and 3 Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48109
The decreased natriuretic action of dopamine in the young
has been attributed to decreased generation of cAMP by the activated renal D1-like receptor. However, sodium/hydrogen exchanger
(NHE) 3 activity in renal brush-border membrane vesicles (BBMV) can be
modulated independent of cytoplasmic second messengers. We therefore
studied D1-like receptor regulation of NHE activity in
BBMVs in 2-, 4-, and 12-wk-old (adult) rats. Basal NHE activity was
least in 2-wk-old compared with 4- and 12-wk-old rats.
D1-like agonist (SKF-81297) inhibition of NHE activity was
also least in 2-wk-old (
1 ± 9%, n = 3) compared with
4 (
15 ± 5%, n = 6)- and 12 (
65 ± 4%,
n = 6)-wk-old rats. The decreased response to the
D1-like agonist in BBMV was not caused by decreased
D1 receptors or NHE3 expression in the young.
Gs
, which inhibits NHE3 activity by itself,
coimmunoprecipitated with NHE3 to the same extent in 2-wk-old and adult
rats. Gs
function was also not impaired in the young
because guanosine 5'-O-(3-thiotriphosphate) decreased NHE
activity to a similar extent in 4-wk-old and adult rats.
G
i-3 protein expression in BBMV also did not change with
age. In contrast, G
expression and the amount of G
that
coimmunoprecipitated with NHE3 in BBMV was greatest in 2-wk-old rats
and decreased with age. G
common antibodies did not affect
D1-like agonist inhibition of NHE activity in adult rats
(8%) but markedly increased it (48%)in 4-wk-old rats. We conclude
that the decreased inhibitory effect of D1-like receptors
on NHE activity in BBMV in young rats is caused, in part, by the
increased expression and activity of the G protein subunit G
/
.
The direct regulation of NHE activity by G protein subunits may be an
important step in the maturation of renal tubular ion transport.
D1 dopamine receptor; sodium-hydrogen exchanger 3; G
/
subunit; renal proximal tubules; ontogeny
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