CHARACTERIZATION AND DISTRIBUTION OF NATRIURETIC PEPTIDE RECEPTORS IN THE RAT UTERUS

Atrial natriuretic peptide (ANP) receptors were characterized in rat uterus. The binding of [I-125]ANP to uterine membranes was completely competed for by increasing concentrations of unlabeled ANP (K-d = 0.39 nM) and brain natriuretic peptide (K-d = 1.24 ans) and partially by C-type natriuretic peptide (CNP; K-d = 80.4 nM), but not by C-ANF. Also, [I-125]Tyr-CNP bound to uterine membranes was completely competed by unlabeled CNP (K-d = 1.12 nM). Cross-linking of [I-125]ANP to uterine membranes revealed the presence of one band of 130 kilodaltons, corresponding to the guanylyl cyclase (GC-A and/or GC-B) subtypes of natriuretic peptide receptors. The presence of messenger RNA coding for genes of both GC-A and GC-B receptors was shown by quantitative reverse transcriptase polymerase chain reaction. Furthermore, ANP and, to a lesser degree, CNP stimulated the production of cGMP in rat uterus. Autoradiographic studies localized the highest binding of [I-125]ANP in the endometrium, whereas [I-125]Tyr-CNP binding was distributed in the endometrium as well as in the myometrium. These results demonstrate that rat uterine ANP receptors are of the guanylyl cyclase-coupled subtypes. The uterus is a target of natriuretic peptides where ANP induces its biological effects through the production of cGMP.