title: Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism.
abstract: A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane. In the present study we compared parathyroid hormone-stimulated adenylate cyclase activity in membrane preparations from the renal cortex of three controls and a patient with pseudohypoparathyroidism. In the pseudohypoparathyroid preparation the Km for ATP was significantly greater and parathyroid hormone elicited markedly diminished adenylate cyclase activity at a subsaturating concentration of ATP. In contrast, the dose-response effect of enzyme activity to parathyroid hormone was the same in the control preparations, and that of the pseudohypoparathyroidism kidney, at a saturating concentration of ATP. The apparent alteration in enzyme kinetics, however, was normalized upon addition of guanosine 5'-triphosphate to the reaction mixtures. These results indicate that the defect in the parathyroid hormone-receptor-adenylate cyclase complex of the renal cell membranes, in our patient with pseudohypoparathyroidism, is an abnormal nucleotide receptor site of decreased activity. Such a defect may result in partial uncoupling of the parathyroid hormone receptor and adenylate cyclase, rendering the organ refractory to hormonal stimulation.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007672:Kidney Cortex / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D011547:Pseudohypoparathyroidism / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D010281:Parathyroid Hormone; D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases