Brown J, Czarnecki A
Physiological Laboratory, Cambridge, United Kingdom.
Am J Physiol. 1990 Jan;258(1 Pt 2):R57-63. doi: 10.1152/ajpregu.1990.258.1.R57.
Displacement of bound 125I-labeled atrial natriuretic peptide-(1-28) [alpha 125I-ANP-(1-28)] by alpha-ANP-(5-28) and porcine brain natriuretic peptide (BNP) was used to map receptors common to these peptides in rat brain by in vitro autoradiography. alpha-125I-ANP bound reversibly to subfornical organ, area postrema, median preoptic, supraoptic and paraventricular nuclei, and arachnoid mater. Binding at these sites was displaced similarly by 1 microM unlabeled alpha-ANP, alpha-ANP-(5-28), and BNP. Binding dissociation constants in the subfornical organ and arachnoid were 4.40 +/- 1.15 and 3.99 +/- 0.86 nM, respectively, for alpha-ANP, and 2.41 +/- 1.11 and 2.23 +/- 1.06 nM, respectively, for BNP. alpha-125I-ANP also bound to choroid plexus. Here 1 microM unlabeled alpha-ANP displaced significantly more radioligand than did 1 microM BNP, and the concentration displacing 50% of bound radioligand was 2.23 +/- 0.78 nM for alpha-ANP and 1.51 +/- 0.67 nM for BNP. alpha-ANP-(5-28) also displaced alpha 125I-ANP at all sites with significantly greater affinity than did unlabeled alpha-ANP. alpha-125I-ANP was not displaced by completely unrelated peptides. Therefore, both atrial and brain natriuretic peptides may be high-affinity ligands at common receptors in some cerebral localities.
利用α-心房钠尿肽(α-ANP)-(5 - 28)和猪脑钠尿肽(BNP)对结合的125I标记心房钠尿肽-(1 - 28) [α125I-ANP-(1 - 28)]的置换作用,通过体外放射自显影技术在大鼠脑中定位这些肽类的共同受体。α125I-ANP可逆性地结合于穹窿下器官、最后区、视前正中核、视上核、室旁核以及蛛网膜。在这些部位,1μM未标记的α-ANP、α-ANP-(5 - 28)和BNP对结合的置换作用相似。在穹窿下器官和蛛网膜中,α-ANP的结合解离常数分别为4.40±1.15 nM和3.99±0.86 nM,BNP的结合解离常数分别为2.41±1.11 nM和2.23±1.06 nM。α125I-ANP也结合于脉络丛。在此处,1μM未标记的α-ANP比1μM BNP置换出的放射性配体显著更多,且使50%结合放射性配体被置换的浓度,α-ANP为2.23±0.78 nM,BNP为1.51±0.67 nM。α-ANP-(5 - 28)在所有部位对α125I-ANP的置换亲和力也显著高于未标记的α-ANP。完全不相关的肽类不能置换α125I-ANP。因此,心房钠尿肽和脑钠尿肽在某些脑区可能都是共同受体的高亲和力配体。