Maack T, Suzuki M, Almeida F A, Nussenzveig D, Scarborough R M, McEnroe G A, Lewicki J A
Department of Physiology, Cornell University Medical College, New York, NY 10021.
Science. 1987 Oct 30;238(4827):675-8. doi: 10.1126/science.2823385.
A ring-deleted analog of atrial natriuretic factor--des[Gln18, Ser19, Gly20, Leu21, Gly22] ANF4-23-NH2 (C-ANF4-23)--binds with high affinity to approximately 99% of ANF receptors in the isolated perfused rat kidney. In this preparation, C-ANF4-23 is devoid of detectable renal effects and does not antagonize any of the known renal hemodynamic and natriuretic actions of biologically active ANF1-28. In contrast, both C-ANF4-23 and ANF1-28 increase sodium excretion and decrease blood pressure in intact anesthetized rats. This apparent contradiction is resolved by the finding that the ring-deleted analog markedly increases plasma levels of endogenous immunoreactive ANF in the rat. The results show that the majority of the renal receptors of ANF are biologically silent. This new class of receptors may serve as specific peripheral storage-clearance binding sites, acting as a hormonal buffer system to modulate plasma levels of ANF.
心房利钠因子的一种环缺失类似物——去[谷氨酰胺18、丝氨酸19、甘氨酸20、亮氨酸21、甘氨酸22]心房利钠因子4 - 23 - NH₂（C - ANF4 - 23）——以高亲和力与离体灌注大鼠肾脏中约99%的心房利钠因子受体结合。在此制备过程中，C - ANF4 - 23没有可检测到的肾脏效应，并且不拮抗生物活性心房利钠因子1 - 28的任何已知肾脏血流动力学和利钠作用。相比之下，C - ANF4 - 23和心房利钠因子1 - 28均可增加完整麻醉大鼠的钠排泄并降低血压。这一明显的矛盾通过以下发现得以解决：这种环缺失类似物可显著提高大鼠体内内源性免疫反应性心房利钠因子的血浆水平。结果表明，心房利钠因子的大多数肾脏受体在生物学上是无活性的。这类新的受体可能作为特定的外周储存 - 清除结合位点，充当一种激素缓冲系统来调节心房利钠因子的血浆水平。
