Inhibition of endothelial cell clearance of atrial natriuretic peptide by cyclic GMP treatment.

In a previous study, we reported that cyclic GMP (cGMP) selectively down-regulates the clearance receptor (C-receptor) for atrial natriuretic peptide (ANP) in the cultured bovine pulmonary artery endothelial (CPAE) cell line. The present study was undertaken in order to examine the effect of cGMP on the internalization of the ANP-receptor complex in CPAE cells. Maximum binding of 125I]APIII to the cells significantly decreased following the treatment with 1 mM 8-bromo-cGMP for 48 or 72 h. Scatchard analysis of the binding assay data from the treated cells showed a decrease in Bmax (616 to 411 fmol/mg protein) without a significant change in Kd. Removal of cell surface-bound APIII by acetic acid revealed that not only the surface binding, but also the internalization of APIII significantly decreased in 8-bromo-cGMP-treated cells, indicating a decrease in receptor-mediated uptake of ANP into the cells. These results suggest that cGMP regulates the clearance of ANP by vascular endothelial cells.