Adrenocorticoid regulation of Na+,K(+)-ATPase in adult rat kidney: effects on post-translational processing and mRNA abundance.
The mechanisms by which adreno-corticoid hormones regulate Na+,K(+)-ATPase in adult kidney were studied in adrenalectomized (Adx) rats. Five days after adrenalectomy, Na+,K(+)-ATPase activity was significantly reduced in the renal cortex homogenate (C = 13.0 +/- 0.8 vs. Adx = 7.1 +/- 0.7 mumol Pi mg-1 protein h-1) and in renal microsomes (C = 30.3 +/- 1.9 vs Adx = 14.6 +/- 1.3 mumol Pi mg-1 protein h-1). Glucocorticoid replacement treatment of adrenalectomized rats with betamethasone (20 micrograms kg-1 body wt twice daily for 5 days) effectively counteracted the observed reduction in Na+,K(+)-ATPase activity. In cortical homogenate the protein level of alpha 1 and beta 1 subunits measured in immunoblots was not significantly different in Adx and control rats, indicating that 5 days after adrenalectomy the alpha 1 and beta 1 subunits were present in renal cortical cells to almost normal extent but could not be assembled into a transmembrane functional unit. In support of this conclusion we found that the protein level of both the alpha 1 and beta 1 subunits was significantly lower (P less than 0.001 for both subunits) in microsomes from Adx than in control rats. The mRNA abundance for alpha 1 and beta 1 subunits were not lower in Adx as compared to control rats 1 and 5 days after surgery. However, if Adx rats were given a single dose of betamethasone (600 micrograms kg-1 body wt), a significant 2-fold increase in both alpha 1 and beta 1 mRNAs was observed (P less than 0.05 for both subunits).(ABSTRACT TRUNCATED AT 250 WORDS)
Celsi
G
G
Department of Paediatrics, St. Göran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Ståhl
J
J
Wang
Z M
ZM
Nishi
A
A
D000315:Adrenalectomy; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D015151:Immunoblotting; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D001623:Betamethasone; D000254:Sodium-Potassium-Exchanging ATPase