AJP - Renal Physiology, Vol 258, Issue 6 1640-F1649, Copyright © 1990 by American Physiological Society
Effect of acidosis on PTH-dependent renal adenylate cyclase in phosphorus deprivation: role of G proteins
E. Bellorin-Font, R. Starosta, C. L. Milanes, C. Lopez, N. Pernalete, J. Weisinger and V. Paz-Martinez
Centro Nacional de Dialisis y Trasplante, Hospital Universitario de Caracas, Venezuela.
These studies examine the regulation of adenylate cyclase in renal cortical
membranes from phosphate-deprived and phosphate-deprived acidotic dogs.
Enzyme stimulation by parathyroid hormone (PTH) was decreased in phosphate
deprivation [Vmax 1,578 +/- 169 vs. 2,581 +/- 219 pmol adenosine
3',5'-cyclic monophosphate (cAMP).mg protein-1 x 30 min-1 in controls, P
less than 0.01]. Metabolic acidosis further decreased PTH-stimulated
activity. Membranes from phosphate-deprived dogs showed a decrease in Gs
alpha-content by cholera toxin-dependent ADP-ribosylation (174 +/- 18
arbitrary units vs. 266.4 +/- 13.6 in controls, P less than 0.01).
Metabolic acidosis further decreased Gs alpha-content, P less than 0.01. Gi
content by pertussis-dependent ADP-ribosylation was also lower in
phosphate-deprived and phosphate-deprived acidotic animals. Gs function was
examined by its property to protect the catalytic unit from inactivation by
N-ethylmaleimide when preincubated with GTP gamma S. In controls,
protection of inactivation was 80% of the maximal activity, whereas in
phosphate deprivation protection was less than 50%. In conclusion,
metabolic acidosis enhances adenylate cyclase resistance to PTH in
phosphate deprivation. These alterations are associated with a decrease in
the content and function of Gs alpha, suggesting a role of Gs in the renal
adaptation to phosphate depletion and acidosis.
