SODIUM STATUS AFFECTS GC-B NATRIURETIC PEPTIDE RECEPTOR MESSENGER-RNA LEVELS, BUT NOT GC-A OR C-RECEPTOR MESSENGER-RNA LEVELS, IN THE SHEEP KIDNEY

1. In humans and experimental animals the natriuresis and diuresis resulting from infusion of atrial natriuretic peptide varies with the sodium status of the subject. Tissue binding studies have suggested that this may be related to changes in the renal receptors for the hormone. 2. In order to establish whether these changes are under transcriptional control, we examined the levels of mRNA for the three natriuretic peptide receptors [GC-A, GC-B and clearance (C) receptors] in renal cortex and medulla from six sodium-loaded, six sodium-depleted and four control sheep. cDNA probes specific to each receptor were generated using the polymerase chain reaction. 3. GC-B receptor mRNA levels were increased approximately two-fold in the renal cortex of sodium-depleted animals, whereas there was no influence on GC-B receptor mRNA levels in the renal medulla. There was no significant difference in mRNA levels for the GC-A and C receptors. 4. At present the role of the GC-B receptor and its natural ligand C-type natriuretic peptide in the control of renal function is unknown. The present experiments imply some intrarenal function for the GC-B receptor and its natural ligand, although the site of any such function, e.g. renal vasculature or tubules, remains unclear. In addition, we have shown that if GC-A and C receptor levels in the sheep are modulated by sodium, the regulation occurs beyond the level of gene transcription.