REGULATION OF ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS IN BRAIN CAPILLARYENDOTHELIAL-CELLS

We performed a systematic study of the regulation of cell surface natr iuretic peptide receptors of cultured bovine brain capillary endotheli al cells (BCEC) and compared them with the regulation in aortic endoth elial (AEC) and adrenal cells. Primary cell cultures were prepared and incubated with 10(-8) M atrial natriuretic peptide (ANP), brain natri uretic peptide (BNP), or the truncated analog, CANP 4-23. The BCEC cel l surface receptors were decreased to less than 33% of baseline within 20 min by ANP and BNP, but the decrease was considerably less in AEC and adrenal cells. CANP 4-23 consistently produced less decrease in su rface receptors. After ANP-induced down regulation, restoration of cel l surface receptors began within 1 h, but took up to 6 h to reach base line. Trypsin treatment of the cells removed the surface receptors and depleted over 70% of the total cellular ANP receptor pool. If the cel ls underwent ANP-induced down regulation prior to trypsin treatment, t he total number of cellular ANP receptors was not decreased by trypsin , implying that ANP caused internalization of surface receptors. There was no change in mRNA expression for the C or clearance receptor in B CEC after 24 h. incubation with either 10(-7) M ANP or CANP 4-23. We c onclude that alterations in the expression of cell surface receptors a re due to recycling of surface receptors within the cells. This implie s that receptor cycling in capillary beds may play an important role i n the maintenance of surface receptors and cellular processing of natr iuretic peptides.