Beaumont K, Tan P K
Department of Medicine, University of California, San Diego, La Jolla 92093.
J Neurosci Res. 1990 Feb;25(2):256-62. doi: 10.1002/jnr.490250215.
The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des[gl18, ser19, gly20, leu21, gly22] ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function (Maack et al.: Science 238:675-678, 1987) and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors (Féthiere et al.: Mol Pharmacol 35:584-592, 1989). ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.
测定了心房利钠肽（ANP）和脑利钠肽（BNP）改变大鼠新皮质星形胶质细胞中环鸟苷酸（cGMP）水平及NaKCl协同转运的能力。在10⁻⁹ - 10⁻⁶ M的浓度范围内，大鼠ANP99 - 126（rANF）、大鼠ANP102 - 126（耳尿肽B）和大鼠ANP103 - 126（心钠素III）刺激cGMP水平升高6至100倍。在该浓度范围的大部分情况下，猪BNP（pBNP）和大鼠BNP（rBNP）的效力为rANF的20% - 90%，不过10⁻⁶ M的pBNP产生的作用比rANF更大。用布美他尼敏感的⁸⁶Rb⁺内流测定的NaKCl协同转运，在星形胶质细胞暴露于10⁻⁶ M的rANF、pBNP或rBNP时未发生改变。pBNP和rBNP，以及大鼠ANP103 - 123（心钠素I）和去[gl18，ser19，gly20，leu21，gly22]ANF4 - 23 - NH₂（C - ANF4 - 23）在星形胶质细胞膜中与特异性¹²⁵I - rANF结合位点强烈竞争，亲和力范围为0.03至0.4 nM，这表明在亚纳摩尔浓度的¹²⁵I - rANF下测定的几乎所有结合位点均为ANP - C（ANF - R2）受体亚型。这些受体被认为具有清除功能（Maack等人：《科学》238：675 - 678，1987），并且可能与一种鸟苷酸环化酶活性相关联，该活性在化学和药理学上与与ANP - A（ANF - R1）受体偶联的活性不同（Féthiere等人：《分子药理学》35：584 - 592，1989）。星形胶质细胞上的ANP受体可能在限制ANP和BNP与参与体液和心血管调节的神经元接触方面发挥作用。
