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Am J Physiol Regul Integr Comp Physiol 278: R931-R936, 2000;
0363-6119/00 $5.00
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Vol. 278, Issue 4, R931-R936, April 2000

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

Xiao Xi Li1, Frederick E. Albrecht1,2, Jean E. Robillard3, Gilbert M. Eisner4, and Pedro A. Jose1,2

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. Gsalpha , which inhibits NHE3 activity by itself, coimmunoprecipitated with NHE3 to the same extent in 2-wk-old and adult rats. Gsalpha 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. Galpha i-3 protein expression in BBMV also did not change with age. In contrast, Gbeta expression and the amount of Gbeta that coimmunoprecipitated with NHE3 in BBMV was greatest in 2-wk-old rats and decreased with age. Gbeta 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 Gbeta /gamma . 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; Gbeta /gamma subunit; renal proximal tubules; ontogeny


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