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单一激肽受体在黄热病蚊的马尔皮基氏小管中向不同的独立生理途径发出信号。

The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito.

机构信息

Dept. of Biomedical Sciences, VRT 8004, Cornell Univ., Ithaca, NY 14853, USA.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R612-22. doi: 10.1152/ajpregu.00068.2010. Epub 2010 Jun 10.

Abstract

In the past, we have used the kinins of the cockroach Leucophaea (the leucokinins) to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using the kinins of Aedes (the aedeskinins), we have found that in isolated Aedes Malpighian tubules all three aedeskinins (1 microM) significantly 1) increased the rate of fluid secretion (V(S)), 2) hyperpolarized the basolateral membrane voltage (V(bl)), and 3) decreased the input resistance (R(in)) of principal cells, consistent with the known increase in the Cl(-) conductance of the paracellular pathway in Aedes Malpighian tubules. Aedeskinin-III, studied in further detail, significantly increased V(S) with an EC(50) of 1.5 x 10(-8) M. In parallel, the Na(+) concentration in secreted fluid significantly decreased, and the K(+) concentration significantly increased. The concentration of Cl(-) remained unchanged. While the three aedeskinins triggered effects on V(bl), R(in), and V(S), synthetic kinin analogs, which contain modifications of the COOH-terminal amide pentapeptide core sequence critical for biological activity, displayed variable effects. For example, kinin analog 1578 significantly stimulated V(S) but had no effect on V(bl) and R(in), whereas kinin analog 1708 had no effect on V(S) but significantly affected V(bl) and R(in). These observations suggest separate signaling pathways activated by kinins. One triggers the electrophysiological response, and the other triggers fluid secretion. It remains to be determined whether the two signaling pathways emanate from a single kinin receptor via agonist-directed signaling or from a differentially glycosylated receptor. Occasionally, Malpighian tubules did not exhibit a detectable response to natural and synthetic kinins. Hypothetically, the expression of the kinin receptor may depend on developmental, nutritional, and/or reproductive signals.

摘要

在过去,我们曾使用蟑螂(Leucophaea)的激肽(leucokinins)来评估激肽肽在黄热病蚊子埃及伊蚊(Aedes aegypti)的马尔皮基氏小管中的利尿作用机制。现在,使用 Aedes(aedeskinins)的激肽,我们发现,在分离的 Aedes 马尔皮基氏小管中,所有三种 aedeskinins(1 microM)都显著地:1)增加了流体分泌率(V(S)),2)超极化了基底外侧膜电压(V(bl)),3)降低了主细胞的输入电阻(R(in)),这与已知的 Aedes 马尔皮基氏小管中旁细胞途径的 Cl(-)电导增加一致。进一步研究的 aedeskinin-III 显著增加了 V(S),EC(50)为 1.5 x 10(-8) M。同时,分泌液中的 Na(+)浓度显著降低,K(+)浓度显著增加。Cl(-)浓度保持不变。虽然三种 aedeskinins 触发了 V(bl)、R(in)和 V(S)的作用,但含有生物活性关键的 COOH 末端酰胺五肽核心序列修饰的合成激肽类似物则显示出不同的作用。例如,激肽类似物 1578 显著刺激了 V(S),但对 V(bl)和 R(in)没有影响,而激肽类似物 1708 对 V(S)没有影响,但显著影响了 V(bl)和 R(in)。这些观察结果表明,激肽激活了不同的信号通路。一种信号通路触发了电生理学反应,另一种信号通路触发了流体分泌。目前尚不清楚这两种信号通路是否是由激肽受体通过激动剂导向的信号或由不同糖基化的受体激活的。偶尔,马尔皮基氏小管对天然和合成激肽没有表现出可检测的反应。从理论上讲,激肽受体的表达可能取决于发育、营养和/或生殖信号。

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