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鸟苷素和尿鸟苷素在离体灌注大鼠肾脏中的利钠和利钾活性

Natriuretic and kaliuretic activities of guanylin and uroguanylin in the isolated perfused rat kidney.

作者信息

Fonteles M C, Greenberg R N, Monteiro H S, Currie M G, Forte L R

机构信息

Clinical Research Unit, Federal University of Ceara and Ceara State University, 60434 Fortaleza, Brazil.

出版信息

Am J Physiol. 1998 Aug;275(2):F191-7. doi: 10.1152/ajprenal.1998.275.2.F191.

DOI:10.1152/ajprenal.1998.275.2.F191
PMID:9691007
Abstract

Guanylin and uroguanylin are novel peptides that activate membrane guanylate cyclases found in the kidney and intestine. We compared the effects of these peptides in the isolated perfused rat kidney. Both peptides are natriuretic and kaliuretic in this preparation. Uroguanylin (0.19-1.9 microM) increased glomerular filtration rate from 0.77 +/- 0.07 to 1.34 +/- 0.3 ml . g-1 . min-1 at the highest concentration. A maximal increase in Na+ excretion was achieved at 0. 66 microM uroguanylin, with a reduction in fractional Na+ reabsorption from 78.7 +/- 1.7 to 58.8 +/- 4.4%. The highest dose of uroguanylin increased kaliuresis by 50%. Osmolar clearance doubled at the highest concentration of uroguanylin tested (P < 0.05). Guanylin also elicited a natriuresis and kaliuresis but appeared to be less potent than uroguanylin. The highest concentration of guanylin (1.3 microM) decreased fractional Na+ reabsorption from 73. 9 +/- 2.4 to 64.5 +/- 4.0%, but lower doses were ineffective. Guanylin stimulated urine K+ excretion at the lowest concentration tested (0.33 microM) without any effect on Na+ excretion. These peptides may influence salt and water homeostasis by biological effects in the kidney that are mediated by the intracellular second messenger, cGMP.

摘要

鸟苷林和尿鸟苷林是新型肽类,可激活肾脏和肠道中的膜鸟苷酸环化酶。我们比较了这些肽类在离体灌注大鼠肾脏中的作用。在该实验准备中,这两种肽类均具有利钠和利尿作用。尿鸟苷林(0.19 - 1.9 microM)在最高浓度时可使肾小球滤过率从0.77±0.07增加至1.34±0.3 ml·g⁻¹·min⁻¹。尿鸟苷林浓度为0.66 microM时,Na⁺排泄量达到最大增加,Na⁺重吸收分数从78.7±1.7%降至58.8±4.4%。尿鸟苷林最高剂量可使尿钾排泄增加50%。在测试的尿鸟苷林最高浓度时,渗透清除率增加了一倍(P < 0.05)。鸟苷林也可引起利钠和利尿作用,但似乎效力低于尿鸟苷林。鸟苷林最高浓度(1.3 microM)可使Na⁺重吸收分数从73.9±2.4%降至64.5±4.0%,但较低剂量无效。鸟苷林在测试的最低浓度(0.33 microM)时刺激尿K⁺排泄,而对Na⁺排泄无任何影响。这些肽类可能通过肾脏中由细胞内第二信使cGMP介导的生物学效应来影响盐和水平衡。

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