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Investigation of the potential involvement of eicosanoid metabolites in anti-diuretic hormone signaling in Rhodnius prolixus

机译:类花生酸代谢产物可能参与抗红景天抗利尿激素信号的研究

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The use of naturally occurring plant-derived compounds for controlling insect pests remains an attractive alternative to potentially dangerous synthetic chemical compounds. One prospective plant-based compound, isoforms of the so-called jack bean urease (JBU) from the jack bean, Canavalia ensiformis, as well a derived peptide, Jaburetox-2Ec, have insecticidal effects on an array of insect species. In the Chagas' disease vector, Rhodnius prolixus, some of the physiological effects attributed to these urease isoforms include inhibition of serotonin (5-HT)-stimulated fluid secretion by the Malpighian tubules (MTs). Here, we investigated whether the effects of these exogenous urease isoforms were targeting the neuroendocrine network involved in the anti-diuretic hormone (RhoprCAPA-2) signaling cascade. We show that pharmacological agents known to interfere with eicosanoid metabolite biosynthesis do not affect RhoprCAPA-2 inhibition of 5-HT-stimulated fluid secretion by MTs. In addition, we demonstrate that RhoprCAPA-2 inhibition of MTs is independent of extracellular or intracellular calcium. Using a heterologous system for analysis of receptor activation, we show that neither JBU nor Jaburetox-2Ec are agonists of the anti-diuretic hormone receptor, RhoprCAPAr1. Finally, activation of the receptor using sub-maximal doses of the natural ligand, RhoprCAPA-2, was not influenced by the presence of either JBU or Jaburetox-2Ec indicating that the urease isoforms do not compete with RhoprCAPA-2 for binding and activation of RhoprCAPAr1. Taken together, these results suggest that at least two distinct mechanisms leading to inhibition of fluid secretion by MTs exist in R. prolixus and, unlike the urease-related effects, the eicosanoid metabolite pathway is not involved in RhoprCAPA-2 mediated anti-diuresis.
机译:使用天然存在的植物来源的化合物防治害虫仍然是潜在危险的合成化合物的诱人替代品。一种来自植物的前瞻性化合物,即来自杰克豆(Canavalia ensiformis)的所谓杰克豆脲酶(JBU)的同工型,以及衍生的肽Jaburetox-2Ec对一系列昆虫具有杀虫作用。在恰加斯氏病病原体Rhodnius prolixus中,归因于这些脲酶同工型的某些生理效应包括由Malpighian小管(MTs)抑制5-羟色胺(5-HT)刺激的液体分泌。在这里,我们调查了这些外源脲酶同工型的作用是否针对抗利尿激素(RhoprCAPA-2)信号级联反应所涉及的神经内分泌网络。我们表明已知干扰类花生酸代谢物生物合成的药理作用不会影响MT对RhoprCAPA-2抑制5-HT刺激的液体分泌。此外,我们证明RhoprCAPA-2对MT的抑制作用独立于细胞外或细胞内钙。使用异源系统分析受体激活,我们表明JBU和Jaburetox-2Ec都不是抗利尿激素受体RhoprCAPAr1的激动剂。最后,JBU或Jaburetox-2Ec的存在不会影响使用亚最大剂量的天然配体RhoprCAPA-2激活受体,这表明脲酶同工型不会与RhoprCAPA-2竞争结合和激活RhoprCAPAr1。综上所述,这些结果表明,至少有两种导致MTs抑制液体分泌的不同机制,并且与脲酶相关的作用不同,类花生酸代谢途径不参与RhoprCAPA-2介导的抗利尿作用。

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