Inhibition of renal adenylate cyclase by plasma from uremic patients.

The native plasma of patients suffering from renal insufficiency inhibited the parathyroid hormone (PTH), the vasopressin (VP) and the NaF-activated adenylate cyclase (AC) in bovine renal plasma membranes. A crude immunoglobulin fraction, prepared by (NH4)2SO4 precipitation, decreased only the hormone, but not the NaF activated AC. Chromatography of the native plasma on a AcA 34 column revealed two peaks inhibiting the PTH and to a lesser extent the VP dependent AC. Only the second peak reduced the NaF stimulated cAMP production. None of the column samples inhibited the isoproterenol stimulated adenylate cyclase in turkey red blood cells. Further purification of the first peak on a Sepharose 6B column confirmed previous results that immunoglobulins may block the PTH receptor in the kidney. Repurification of the second peak of inhibition on a Bio-Gel P10 column suggested that small peptides crossreacting in the radioimmunoassay for PTH may desensitize the hormonal receptor.