Weir M L, Pang S C, Flynn T G
Department of Biochemistry, Queen's University, Kingston, Canada.
Regul Pept. 1993 Sep 22;47(3):291-305. doi: 10.1016/0167-0115(93)90396-p.
Binding studies, affinity cross-linking and guanylate cyclase assays allowed a comparison of receptors with which the rat forms of atrial/A-type natriuretic peptide (rANP), brain/B-type natriuretic peptide (rBNP) and C-type natriuretic peptide (rCNP) interact in rat kidney cortex and lung. This work represents the first study in which the rat form of BNP (= rBNP-45/iso-rANP(1-45)) has been used as a radiolabelled tracer to further characterize its receptors in these tissues. In addition, these studies stress the use of the same species of natriuretic peptide and assay system, an important experimental des ign given that BNPs show species-specific differences in structure. rBNP-45 bound with lower affinity to rANP (99-126) receptors, namely guanylate cyclase-linked receptor(s) and C-receptor. No receptor which interacted with only rBNP-45 was detectable in lung and kidney cortex. Since rBNP-45 interacted preferentially with the C-receptor and was less potent than rANP(99-126) in stimulating glomerular guanylate cyclase, rBNP-45 may signal through another second messenger in addition to cyclic GMP. Work with truncated analogues of this hormone pinpointed regions of this peptide which may contribute to receptor binding affinity and guanylate cyclase activation. CNP-22 bound to only a subset of ANP receptors and was least effective in stimulating glomerular guanylate cyclase, suggesting a differential mode of action from ANP.
结合研究、亲和交联和鸟苷酸环化酶测定，使得对大鼠心房/ A型利钠肽（rANP）、脑/ B型利钠肽（rBNP）和C型利钠肽（rCNP）在大鼠肾皮质和肺中相互作用的受体进行比较成为可能。这项工作是首次将大鼠形式的BNP（= rBNP - 45 /异rANP(1 - 45)）用作放射性标记示踪剂，以进一步表征其在这些组织中的受体。此外，这些研究强调了使用同一种利钠肽和测定系统，鉴于BNP在结构上存在物种特异性差异，这是一个重要的实验设计。rBNP - 45与rANP（99 - 126）受体，即鸟苷酸环化酶偶联受体和C受体的结合亲和力较低。在肺和肾皮质中未检测到仅与rBNP - 45相互作用的受体。由于rBNP - 45优先与C受体相互作用，并且在刺激肾小球鸟苷酸环化酶方面比rANP(99 - 126)效力更低，rBNP - 45除了通过环磷酸鸟苷外，可能还通过另一种第二信使发出信号。对这种激素的截短类似物的研究确定了该肽可能有助于受体结合亲和力和鸟苷酸环化酶激活的区域。CNP - 22仅与一部分ANP受体结合，并且在刺激肾小球鸟苷酸环化酶方面效果最差，这表明其作用方式与ANP不同。
