Giannessi D, Andreassi M G, Del Ry S, Clerico A, Colombo M G, Dini N
CNR Institute of Clinical Physiology, Pisa, Italy.
J Endocrinol Invest. 2001 Jan;24(1):8-16. doi: 10.1007/BF03343802.
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.
血小板上的利钠肽结合位点被推测可作为清除受体;然而,该受体的功能尚无明确界定。本研究的目的是:1)通过原创性竞争研究来表征人血小板中的利钠肽受体;2)评估这些结合位点可能存在的年龄调节情况,因为已观察到老年人中ANP清除延迟。125I-ANP与完整血小板的结合被h-ANP、h-BNP、h-CNP以及清除受体的选择性配体c-ANP完全抑制。IC50值分别为0.089±0.029、0.703±0.104、1.19±0.13、3.84±0.04 nmol/l,均值±标准误(与其他利钠肽相比,h-ANP的IC50值p<0.001)。这一关于人血小板中利钠肽受体选择性的观察结果为血小板上存在清除受体提供了新证据。在对照组受试者中,Kd为34.6±4.0 pmol/l,Bmax为13.6±0.92 fmol/10⁹血小板(均值±标准误)(n=46,平均年龄41.7±2.1岁)。与较年轻组(n=21,平均年龄28.0±0.87岁)相比,老年受试者(n=25,平均年龄53.2±1.5岁)的Bmax显著降低:分别为11.4±1.1与16.1±1.4 fmol/10⁹细胞,p=0.0096;此外,观察到Bmax与受试者年龄之间存在显著的负相关关系。这一观察结果表明,随着年龄增长,利钠肽清除可能减少,这与利钠肽血浆水平显著升高相关。