Natriuretic peptide binding sites on platelets have been hypothesized to act as clearance receptors; however, there is no clear definition of the function of this receptor. The aim of the study was: 1) to characterize natriuretic peptide receptors in human platelets by original competition study; 2) to evaluate a possible age modulation of these binding sites, since a delayed clearance of ANP in the elderly has been observed. The binding of 125I-ANP to intact platelets was completely inhibited by h-ANP, h-BNP, h-CNP and c-ANP, the selective ligand of the clearance receptor. IC50 values were 0.089+/-0.029, 0.703+/-0.104 and 1.19+/-0.13, 3.84+/-0.04 nmol/l, mean+/-SE, respectively (p<0.001 for IC50 value of h-ANP compared to the other natriuretic peptides). This observation on the receptor selectivity of natriuretic peptides in human platelets provides new evidence for the presence of the clearance receptor on platelets. In control subjects the Kd was 34.6+/-4.0 pmol/l and Bmax 13.6+/-0.92 fmol/10(9) platelets (mean+/-SE), (no.=46, mean age 41.7+/-2.1 years). Bmax was significantly reduced in older subjects (no.=25, mean age 53.2+/-1.5 years) with respect to the younger group (no.=21, mean age 28.0+/-0.87 years): 11.4+/-1.1 vs 16.1+/-1.4 fmol/10(9) cells, p=0.0096, respectively; moreover, a significant inverse relationship between Bmax and the subject's age was observed. This observation suggests a possible reduction of the natriuretic peptide clearance with aging, associated to a significant increase of plasma levels of natriuretic peptides.