Collaborative Project: Mosquito Diuretic Peptides: Peptide Chemistry, In Vitro Physiology and In Vivo Endocrinology

就数量而言，昆虫是地球上最成功的物种。没有人否认昆虫的许多有益活动，例如，在重要经济作物的授粉，丝绸的生产，以及最近的生物害虫控制（一种昆虫捕食另一种昆虫）。每个人都知道昆虫潜在的破坏性影响。众所周知，昆虫会摧毁整个作物，造成世界饥饿。昆虫也被认为是血液传播致命疾病的可怕载体，如黄热病、疟疾和象皮病。自从《圣经》时代（蝗虫的大灭绝）以来，人们就一直试图对付昆虫对人类的不良影响。在现代，最成功的方法是使用杀虫剂；但是，正如我们现在所了解的那样，杀虫剂对人和动物都有严重的不良副作用。出于这个原因，需要除虫害控制之外的其他方法。目前的提议标志着一种新方法的探索，通过尝试干扰昆虫正常的盐和水预算。将在吸血的黄热病蚊子（埃及伊蚊）中采用这种方法。交配后不久，雌蚊子就会寻找血餐。她需要血液来为她的卵子获取营养和蛋白质。找到来源后，雌性黄热病蚊子会狼吞虎咽，吃下相当于自己体重2-3倍的食物。如此重的食物量阻止了蚊子飞走，从而威胁到繁殖的成功（她必须找到一个池塘产卵）和个人的灾难（被拍打）。为了保证前者和避免后者，她必须保持飞行能力和机动性，即通过迅速消除不必要的重量，特别是血中不需要的盐和水部分。她通过一种激素，所谓的利尿剂，利钠激素来做到这一点。在即将到来的资助期内，pi计划纯化和分离这种激素，了解其结构并尝试合成它。这项工作将在德克萨斯州农工大学的多肽化学家Hayes博士的实验室进行。与此同时，康奈尔大学的贝恩巴赫博士（运输生理学家）将研究蚊子的肾脏在激素的影响下如何正常工作。昆虫内分泌学家哈格多恩博士（亚利桑那大学）的实验室将研究这种激素是如何在蚊子体内释放的，它是在哪里制造和储存的，以及它会影响肾脏以外的哪些器官。通过破坏昆虫体内正常的盐和水平衡来控制害虫的三个潜在目标地点将被调查：1)在需要保存盐和水的时候，给予合成激素，导致它们失去盐和水；2)干扰正常的肾功能，例如阻止激素的作用，从而影响繁殖成功；3)在昆虫需要激素的时候，通过抑制激素的产生或释放，破坏盐和水平衡的正常反馈回路。

In sheer numbers, insects are the most successful species on earth. No one denies the many beneficial activities of insects as, for example, in the pollination of economically important crops, the production of silk, and most recently biological pest control (one insect predating on another). Everybody also knows about the potentially devastating effects of insects. Insects have been known to wipe out entire crops, contributing to world hunger. Insects are also known as the dreadful bearers of blood borne fatal diseases such as yellow fever, malaria, and elephantiasis. Since biblical time (the flight of locust) men have tried to cope with the undesirable impacts of insects on mankind. In modern times the most successful approach has been the use of pesticides; but pesticides - as we are now learning - have serious undesirable side-effects on man and animal alike. For this reason alternatives to insect control are needed. The present proposal marks the exploration of a new approach via attempts to interfere in the normal salt and water budget of the insect. This approach will be pursued in the blood-feeding yellow-fever mosquito (Aedes aegypti). Shortly after mating the female mosquito seeks a bloodmeal. She needs blood in order to obtain nutrients and proteins for her eggs. Having found a source, the female yellow-fever mosquito gorges herself, taking a meal 2-3 times her own body weight| Such a heavy payload prevents the mosquito from flying away, thereby threatening reproductive success (she must find a pond to deposit her eggs) and personal calamity (a swat). To guarantee the former and to avoid the latter, she must maintain flight capability and maneuverability, namely by quickly eliminating unwanted weight, in particular the unwanted salt and water portion of the bloodmeal. This she does by way of a hormone, the so-called diuretic, natriuretic hormone. In the upcoming grant period the PIs plan to purify and isolate this hormone, learn its structure and attempt to synthesize it. This work will be done in the laboratory of a peptide chemist, Dr. Hayes of Texas A&M University. At the same time Dr. Beyenbach (a transport physiologist) at Cornell University will study how the kidney in the mosquito works normally and under the influence of the hormone. And the laboratory of the insect endocrinologist, Dr. Hagedorn (University of Arizona) will investigate how the hormone is released in the mosquito, where it is made and stored, and what organs other than the kidney it affects. Three potential target sites for pest control via disrupting normal salt and water balance in the insect will be investigated: 1) by giving synthetic hormone causing the insect to lose salt and water when they need to be conserved, 2) by interfering with normal kidney function, e.g. preventing the action of the hormone and thereby reproductive success, and 3) by disrupting the normal feedback loop of salt and water balance by inhibiting the production or the release of the hormone, when the insects need the hormone.