Expression and regulation of ANP receptor subtypes in rat renal glomeruli and papillae

The expression and regulation of atrial natriuretic peptide (ANP) receptor subtypes were examined in rat renal glomeruli and papillae. In glomeruli, approximately two-thirds of ANP binding sites represented guanylate cyclase-uncoupled ANP clearance receptors (ANPc) with a molecular mass of 64 kDa under reducing conditions. The remainder of glomerular ANP binding sites represented guanylate cyclase-coupled ANP receptors (ANPGC) with a molecular mass of 130 kDa. In rat papillae, only the 130-kDa ANPGC was expressed. In rats adapted to a low-salt diet, saline loading or acute ANP infusion resulted in a decrease in ANPC density, a difference that was not detected when glomeruli were first acidwashed to remove endogenous ANP, indicating that apparent regulation of ANPC reflected prior occupancy by endogenous ANP. Densities of glomerular ANPC and ANPGC were similar in spontaneously hypertensive rats (SHR) compared with those of the Wistar-Kyoto (WKY) controls. However, elimination of prior receptor occupancy revealed a significantly greater expression of glomerular ANPC in SHR compared with WKY rats, without significant differences in the density of the glomerular or papillary ANPGC subtype. The failure of the ANPGC subtype to be regulated may account for our previously reported findings that dietary salt intake does not affect glomerular ANP-stimulated guanosine-3',5'-cyclic monophosphate accumulation despite apparent regulation of ANP receptor density. Whether the increased expression of the ANPC subtype in SHR represents a primary defect or results from induction of ANP clearance receptor expression remains to be determined.