Effect of acidosis on PTH-dependent renal adenylate cyclase in phosphorus deprivation: role of G proteins.
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.
Bellorin-Font
E
E
Centro Nacional de Dialisis y Trasplante, Hospital Universitario de Caracas, Venezuela.
Starosta
R
R
Milanes
C L
CL
Lopez
C
C
Pernalete
N
N
Weisinger
J
J
Paz-Martinez
V
V
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000643:Ammonium Chloride; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000378:metabolism / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D037342:Pertussis Toxin; D010758:Phosphorus / Q000172:deficiency*; D012969:Sodium Fluoride / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D006150:Guanine Nucleotides; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D000643:Ammonium Chloride; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D010758:Phosphorus; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008345:Manganese; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium; D005033:Ethylmaleimide