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The phosphaturic action of parathyroid hormone (PTH) is blunted during metabolic acidosis. Previous studies suggest that the activation of renal cortical adenylate cyclase by PTH is decreased under this condition. However, the mechanisms underlying the defect are not completely defined. The present studies were designed to examine the interaction of PTH with its receptor-adenylate cyclase system in basolateral cortical membranes from dogs with metabolic acidosis. Chronic metabolic acidosis was induced in seven normal dogs. Venous blood pH decreased to 7.21 +/- 0.01 and serum bicarbonate to 12.58 +/- 0.32 meq/liter. In seven control dogs blood pH was 7.38 +/- 0.002 and serum bicarbonate was 20.14 +/- 0.26 meq/liter. The kidneys were surgically removed and basolateral membranes were prepared by differential centrifugation and ultracentrifugation in discontinuous sucrose density gradients for studies of adenylate cyclase activity and hormone-receptor binding. Metabolic acidosis resulted in a significant decrease in PTH-dependent adenylate cyclase activity (Vmax 2,119 +/- 150 pmol cAMP X mg prot-1 .30 min-1 vs. 3,548 +/- 116 in the controls). The PTH concentration giving half-maximal activation of adenylate cyclase was unchanged. However, PTH-receptor binding showed similar affinity and binding capacity in both groups of membranes. Basal enzyme activity was also similar. In the presence of the GTP analogue 5'-guanylylimidodiphosphate, PTH-dependent adenylate cyclase activity remained markedly decreased in the acidotic dog membranes compared with the controls. The ability of NaF to stimulate enzyme activity was also depressed in the membrane of acidotic dogs. Enzyme activity in the presence of Mn2+ was similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
January 1985,
The American journal of physiology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
May 1982,
The American journal of physiology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
March 1985,
Endocrinology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
June 1990,
The American journal of physiology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
October 1981,
The American journal of physiology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
August 1984,
Endocrinology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
January 1983,
Advances in biochemical psychopharmacology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
January 1980,
Advances in experimental medicine and biology,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
October 1976,
Biochemical and biophysical research communications,
E Bellorin-Font, and
J Humpierres, and
J R Weisinger, and
C L Milanes, and
V Sylva, and
V Paz-Martinez
May 1985,
Calcified tissue international,
