Deficient adenylate cyclase regulatory protein in renal membranes from a patient with pseudohypoparathyroidism.
Recent studies have established that some patients with pseudohypoparathyroidism have a deficiency of the adenylate cyclase regulatory protein (the G unit) in plasma membranes from erythrocytes, platelets, and fibroblasts. We have directly measured the activity of the G unit in renal membranes from a patient with pseudohypoparathyroidism who, in addition to parathyroid hormone resistance, has resistance to thyrotropin and gonadotropins. Erythrocyte membrane G unit activity was 57% that of control erythrocyte membranes. Lubrol PX extracts of renal membranes had only 30% of the G unit activity of control renal membrane extracts, whether assayed with sodium fluoride or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S). In cholate extracts, the G unit activity was 37 and 48% of control with fluoride or GTP-gamma-S, respectively. Cholera toxin-dependent incorporation of [32P]ADP-ribose into the 42,000-Mr subunit of the G unit was decreased in renal membranes from the patient compared with control renal membranes. The data demonstrate that the membrane G unit deficiency in pseudohypoparathyroidism extends to the cells of a clinically relevant parathyroid hormone target tissue.
D000262:Adenylyl Cyclases / Q000172:deficiency*; D000293:Adolescent; D004910:Erythrocyte Membrane / Q000201:enzymology; D005260:Female; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D008970:Molecular Weight; D011547:Pseudohypoparathyroidism / Q000201:enzymology*
D000262:Adenylyl Cyclases