title: Effect of the Hyp mutation and diet-induced hyperparathyroidism on renal parathyroid hormone- and forskolin-stimulated adenosine 3',5'-monophosphate production and brush border membrane phosphate transport.
abstract: The present study was undertaken to investigate the effect of the Hyp mutation and diet-induced hyperparathyroidism on renal responsiveness to PTH and forskolin and to determine whether the renal brush border membrane phosphate transport defect is expressed in the vitamin D- and calcium-deficient Hyp mouse. Our results indicate that PTH is a potent activator of cAMP synthesis in renal slices obtained from vitamin D-replete normal mice and Hyp littermates. However, in the mutants, the amount of cAMP produced in response to similar concentrations of PTH (0.005-5 U/ml) is 55% of normal (P = 0.0076). PTH-dependent cAMP synthesis is significantly reduced in both normal and Hyp mice fed the vitamin D-deficient low calcium diet, and under these conditions, genotype differences are no longer apparent. In contrast, forskolin-stimulated cAMP production is identical in vitamin D-replete normal and mutant mice. Furthermore, cAMP accumulation in response to forskolin is not decreased by diet-induced hyperparathyroidism in either genotype. Vitamin D and calcium deprivation results in a significant decrease in renal brush border membrane Na+-dependent phosphate transport in both genotypes, and under these conditions, the phosphate transport defect persists in Hyp mice. Finally, vitamin D and calcium deprivation has no effect on renal brush border membrane alkaline phosphatase activity. The present results suggest that the catalytic subunit of adenylate cyclase is intact in the mutant strain and that the blunted renal response to PTH in vitamin D-replete Hyp mice as well as in vitamin D- and calcium-deficient mice may be due to uncoupling of the PTH-receptor-adenylate cyclase system. The data also suggest that the expression of the renal phosphate transport defect in Hyp mice is independent of PTH status and alkaline phosphatase activity.
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006961:Hyperparathyroidism / Q000503:physiopathology*; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D008871:Microvilli / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D005576:Colforsin; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases