G beta regulation of Na/H exchanger-3 activity in rat renal proximal tubules during development

The decreased natriuretic action of dopamine in the young has been attribut ed to decreased generation of cAMP by the activated renal D-1-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 activi ty in BBMVs in 2-, 4-, and 12-wk-old (adult) rats. Basal NHE activity was l east 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 D-1 receptors or NHE3 expression in the young. G(s)alpha, whi ch inhibits NHE3 activity by itself, coimmunoprecipitated with NHE3 to the same extent in 2-wk-old and adult rats. G(s)alpha function was also not imp aired in the young because guanosine 5'-O-(3-thiotriphosphate) decreased NH E activity to a similar extent in 4-wk-old and adult rats. G alpha(i-3) pro tein expression in BBMV also did not change with age. In contrast, GP expre ssion and the amount of Gp that coimmunoprecipitated with NHE3 in BBMV was greatest in 2-wk-old rats and decreased with age. GP common antibodies did not affect D1-like agonist inhibition of NHE activity in adult rats (8%) bu t markedly increased it (48%)in 4-wk-old rats. We conclude that the decreas ed inhibitory effect of )l-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 beta/gamma. The direct regulation of NHE activity by G pr otein subunits may be an important step in the maturation of renal tubular ion transport.