NATRIURETIC PEPTIDE RECEPTORS IN THE FETAL-RAT

In vitro autoradiography of rat fetuses from embryonic days 12-19 (E12 -E19) showed widespread high-affinity specific binding sites for natri uretic peptides. The sites on E16 somites avidly bound C-type natriure tic peptide [CNP-(1-22)] as well as C-ANP, a synthetic ligand that sel ects the C-type natriuretic peptide receptor (NPR-C). Most semitic bin ding sites had high affinity for atrial natriuretic peptide [ANP-(1-28 )], confirming their resemblance to NPR-C. A few had a lower apparent affinity for ANP-(1-28), suggesting that they might be NPR-B. CNP-(1-2 2) was more powerful than ANP-(1-28) as an agonist of guanosine 3',5'c yclic monophosphate production in somites, and ATP augmented the actio n of CNP-(1-22). These observations further suggest the presence of NP R-B. However, with crosslinking of 3-[I-125]iodo-O-tyrosyl rat CNP-(1- 22) to semitic membranes followed by sodium dodecyl sulfate-polyacryla mide gel electrophoresis, only a single 64-kDa binding protein was det ected under reducing conditions. This is not consistent with intact si milar to 120-kDa NPR-B. In vitro autoradiography of the binding of nat riuretic peptides to E16 liver implied the presence of NPR-A and NPR-C -like receptors. Hepatic guanosine 3',5'-cyclic monophosphate producti on was most powerfully stimulated by ANP-(1-28), as expected for NPR-A . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also ident ified NPR-A and NPR-C-like proteins in E16 hepatic membranes. Thus dif ferent NPRs are expressed by specific fetal tissues. This may be devel opmentally significant.