Castro R, Leake R D, Ervin M G, Ross M G, Fisher D A
Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance 90509.
Pediatr Res. 1991 Jul;30(1):45-9. doi: 10.1203/00006450-199107000-00009.
Atrial natriuretic factor (ANF) has been identified in fetal and newborn mammals, and considerable data regarding fetal ANF metabolism are available. However, there is limited information concerning ANF receptors or receptor ontogenesis in developing mammals. We measured ANF receptor binding capacity, affinity, and ANF-induced cyclic GMP (cGMP) generation in isolated renal glomeruli from fetal (29 d gestation, term = 31 d), newborn (3 d), juvenile (28 d), and adult rabbits. The (mean +/- SEM) glomerular receptor binding capacity values for ANF in fetal and newborn animals (10 +/- 1 and 12 +/- 3 fmol/mg protein) were similar and significantly lower than the values for juvenile and adult animals (30 +/- 8 and 74 +/- 15 fmol/mg protein, respectively). In contrast, there were no significant differences in ANF receptor affinity values or dose-dependent increases in ANF-stimulated cGMP generation among the age groups studied. In competition studies, we observed effective displacement of 125I-ANF by C-ANF4-23, a ring-deleted ANF analogue, in adult, juvenile, and newborn glomeruli; however, C-ANF displaced only about 50% of the 125I-ANF in fetal tissue. The addition of C-ANF did not elicit cGMP generation, nor did C-ANF affect ANF-induced cGMP generation in fetal, newborn, or adult glomeruli. These results indicate that 1) the ANF receptor-guanylate cyclase system is intact in 29-d fetal rabbit glomeruli, and 2) the ANF-induced cGMP formation is similar in fetal and adult animals, whereas receptor binding capacity is relatively higher in adult glomeruli. These results suggest a higher proportion of nonguanylate cyclase-coupled ANF receptors in the mature rabbit.
在胎儿和新生哺乳动物中已鉴定出心钠素（ANF），并且有大量关于胎儿ANF代谢的数据。然而，关于发育中的哺乳动物的心钠素受体或受体个体发生的信息有限。我们测量了来自胎儿（妊娠29天，足月为31天）、新生（3天）、幼年（28天）和成年兔的离体肾肾小球中心钠素受体的结合能力、亲和力以及心钠素诱导的环磷酸鸟苷（cGMP）生成。胎儿和新生动物肾小球中心钠素的（平均±标准误）受体结合能力值（分别为10±1和12±3 fmol/mg蛋白质）相似，且显著低于幼年和成年动物的值（分别为30±8和74±15 fmol/mg蛋白质）。相比之下，在所研究的年龄组中，心钠素受体亲和力值或心钠素刺激的cGMP生成的剂量依赖性增加没有显著差异。在竞争研究中，我们观察到在成年、幼年和新生肾小球中，环缺失的心钠素类似物C-ANF4-23能有效取代125I-ANF；然而，C-ANF仅能取代胎儿组织中约50%的125I-ANF。添加C-ANF不会引发cGMP生成，也不会影响胎儿、新生或成年肾小球中心钠素诱导的cGMP生成。这些结果表明：1）在妊娠29天的胎儿兔肾小球中，心钠素受体-鸟苷酸环化酶系统是完整的；2）胎儿和成年动物中心钠素诱导的cGMP形成相似，而成年肾小球中的受体结合能力相对较高。这些结果表明，成熟兔中非鸟苷酸环化酶偶联的心钠素受体比例更高。
