Vasotocin analogues with selective natriuretic, kaliuretic and antidiuretic effects in rats

Regulatory Peptides Pub Date : 2013-08-10 DOI:10.1016/j.regpep.2013.06.013

Anna V. Kutina, Anna S. Marina, Elena I. Shakhmatova, Yury V. Natochin

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引用次数: 7

Abstract

The aim of the present study was an investigation of mechanisms mediating selective effect of vasotocin analogues on water, sodium, and potassium excretion. We tested vasotocin analogues: Mpa¹-vasotocin (dAVT), Mpa¹-Arg⁴-vasotocin (dAAVT) and Mpa¹-DArg⁸-vasotocin (dDAVT). The effects on water, sodium, and potassium transport were evaluated in experiments using normal and water-loaded Wistar rats. It was shown that all tested peptides exerted antidiuretic activity. Vasotocin and dAVT induced natriuresis and kaliuresis in rats. V_1a agonist (Phe²-Ile³-Orn⁸-vasopressin) reproduced the renal effects of dAVT on sodium and potassium excretion but not on water reabsorption. dAAVT, dDAVT and V₂ agonist (desmopressin) induced kaliuresis without any effect on sodium excretion. Natriuresis was associated with increase in cGMP excretion, whereas kaliuresis was correlated with rise of cAMP excretion. V_1a antagonist (Pmp¹-Tyr(Me)²-vasopressin) significantly reduced the dAVT-stimulated natriuresis and did not influence on urinary potassium excretion. V₂ antagonist (Pmp¹-DIle²-Ile⁴-vasopressin) significantly reduced the dAVT- and dAAVT-induced kaliuresis. It is assumed that effects of the nonapeptides on sodium and potassium transport are independent of their antidiuretic activity and mediated by different subtypes of V receptors (the V_1a or V_1a-like receptor for natriuretic effect and V₂ or V₂-like one for kaliuretic). In accordance to the data obtained, there is a possibility of selective regulation of renal water reabsorption and urinary sodium and potassium excretion with involvement of neurohypophysial hormones.

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血管催产素在大鼠中具有选择性利钠、利尿和抗利尿作用的类似物

本研究的目的是研究血管催产素类似物对水、钠和钾排泄的选择性作用机制。我们测试了催产素类似物:mpa1 - vaso催生素(dAVT)， mpa1 - arg4 - vaso催生素(dAAVT)和mpa1 - darg8 - vaso催生素(dDAVT)。对水、钠、钾转运的影响分别用正常和载水Wistar大鼠进行实验。结果表明，所有被测肽均具有抗利尿活性。血管催产素和dAVT诱导大鼠尿钠和尿钾。V1a激动剂(phe2 - ile3 - orn8 -血管加压素)再现了dAVT对钠和钾排泄的肾脏影响，但对水的再吸收没有影响。dAAVT、dDAVT和V2激动剂(去氨加压素)诱导钾尿症，对钠排泄无影响。钠尿症与cGMP排泄增加有关，而钾尿症与cAMP排泄增加有关。V1a拮抗剂(Pmp1-Tyr(Me)2-血管加压素)可显著降低davt刺激的尿钠，对尿钾排泄无影响。V2拮抗剂(pmp1 - dile2 - ile4 -血管加压素)可显著降低dAVT-和daavt诱导的尿钾。假设非肽对钠和钾转运的影响独立于其抗利尿活性，并由不同亚型的V受体介导(利钠作用的V1a或V1a样受体和利尿作用的V2或V2样受体)。根据所获得的资料，有可能在神经垂体激素的参与下，选择性地调节肾脏水重吸收和尿钠钾排泄。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Regulatory Peptides 医学-内分泌学与代谢

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2 months

期刊介绍： Regulatory Peptides provides a medium for the rapid publication of interdisciplinary studies on the physiology and pathology of peptides of the gut, endocrine and nervous systems which regulate cell or tissue function. Articles emphasizing these objectives may be based on either fundamental or clinical observations obtained through the disciplines of morphology, cytochemistry, biochemistry, physiology, pathology, pharmacology or psychology.