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首页> 外文期刊>American Journal of Physiology >Renal effects of serine-7 analog of lymphoguanylin in ex vivo rat kidney.
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Renal effects of serine-7 analog of lymphoguanylin in ex vivo rat kidney.

机译：淋巴鸟苷蛋白丝氨酸7类似物在离体大鼠肾脏中的肾脏作用。

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Guanylin and uroguanylin compose a family of natriuretic, diuretic, and kaliuretic peptides that bind to and activate apical membrane receptor guanylyl cyclase signaling molecules in renal and intestinal epithelia. Recently, a complementary DNA encoding an additional member of the guanylin family of cGMP-regulating peptides was isolated from lymphoid tissues of the opossum and was termed lymphoguanylin (LGN). A peptide analog of opossum LGN was synthesized containing a single disulfide bond with the internal cysteine-7 replaced by a serine residue (LGN(Cys7-->Ser7)). The biological activity of LGN(Ser) was tested by using a cGMP bioassay with cultured T84 (human intestinal) cells and opossum kidney (OK) cells. LGN(Ser) has potencies and efficacies for activation of cGMP production in the intestinal and kidney cell lines that are 100- and 1,000-fold higher than LGN, respectively. In the isolated perfused rat kidney, LGN(Ser) stimulated a maximal increase in fractional Na+ excretion from 24.8 +/- 3.0 to 36.3 +/- 3.3% 60 min after administration and enhanced urine flow from 0.15 +/- 0.01 to 0.24 +/- 0.01 ml. g(-1). min(-1). LGN(Ser) (0.69 microM) also increased fractional K+ excretion from 27.3 +/- 2.3 to 38.0 +/- 3.0% and fractional Cl- excretion from 26.1 +/- 0.8 to 43.5 +/- 1.9. A ninefold increase in the urinary excretion of cGMP from 1.00 +/- 0.04 to 9.28 +/- 1.14 pmol/ml was elicited by LGN(Ser), whereas cAMP levels were not changed on peptide administration. These findings demonstrate that LGN(Ser), which contains a single disulfide bond like native LGN, activates guanylyl cyclase-C (GC-C) receptors in T84 and OK cells and may be very helpful in studying the physiological importance of activation of GC-C in vivo. LGN(Ser) also exhibits full activity in the isolated perfused kidney equivalent to that observed previously with opossum uroguanylin, suggesting a physiological role for LGN in renal function. Thus the single amino acid substitution enhances the activity and potency of LGN.
机译：鸟苷蛋白和尿鸟苷蛋白组成一类利尿钠，利尿和利尿钠肽，它们结合并激活肾和肠上皮中的顶膜受体鸟苷酰环化酶信号分子。最近，从负鼠的淋巴组织中分离出编码cGMP调节肽的鸟苷蛋白家族另一成员的互补DNA，被称为淋巴鸟苷蛋白（LGN）。合成了负鼠LGN的肽类似物，该肽类似物包含一个单二硫键，其内部半胱氨酸7被丝氨酸残基取代（LGN（Cys7-> Ser7））。 LGN（Ser）的生物学活性通过使用cGMP生物测定法与培养的T84（人肠）细胞和负鼠肾（OK）细胞进行了测试。 LGN（Ser）具有激活肠和肾细胞系中cGMP产生的能力和功效，分别比LGN高100倍和1,000倍。在分离的大鼠肾脏中，LGN（Ser）刺激60分钟后Na +排泄分数从24.8 +/- 3.0最大增加到36.3 +/- 3.3％，尿流从0.15 +/- 0.01增大到0.24 + / -0.01毫升g（-1）。 min（-1）。 LGN（Ser）（0.69 microM）还将K +排泄分数从27.3 +/- 2.3增加到38.0 +/- 3.0％，Cl-排泄分数从26.1 +/- 0.8增加到43.5 +/- 1.9。 LGN（Ser）引起cGMP尿排泄量从1.00 +/- 0.04增加到9.28 +/- 1.14 pmol / ml九倍，而肽给药后cAMP水平不变。这些发现表明，LGN（Ser）像天然LGN一样包含单个二硫键，可以激活T84和OK细胞中的鸟苷酸环化酶C（GC-C）受体，可能对研究激活GC-C的生理重要性非常有帮助。 C体内。 LGN（Ser）在分离的灌注肾脏中也表现出与先前用负鼠尿鸟苷所观察到的完全相同的活性，表明LGN在肾脏功能中具有生理作用。因此，单个氨基酸取代增强了LGN的活性和效力。

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