Malpighian Tubule Transport Physiology: Mechanisms and Regulation

当溶质和水通过上皮组织（如肠）运输时，它们可能采取两种途径中的一种：通过细胞和/或细胞之间。到目前为止，通过细胞的运输已经得到了非常详细的研究。我们对跨细胞转运及其调控的良好理解有助于我们理解动物对淡水和盐水的适应机制，它导致了囊性纤维化分子缺陷的发现，并有助于新药物（利尿剂）的开发。细胞间的运输机制现在才刚刚开始受到重视。在之前的NSF奖励期间，PI实验室在这个方向上取得了重大进展：首次证明了细胞外肽（白细胞素，一种神经激素）调节细胞外的运输途径。这条通路是否在细胞之间，即所谓的细胞旁通路，是这项工作继续进行的第一个也是最重要的目标。第二个目的是详细检查位于面向肾脏尿侧的细胞膜上的离子泵。第三个目标是发现参与运输调节的新激素。这项工作是在分离的昆虫肾脏中完成的，即黄热病蚊子的所谓马尔比氏小管。

When solutes and water are transported across epithelial tissues such as the intestine, they may take one of two pathways: through cells and/or between cells. To this date transport through cells has been studied in enormous detail. Our good understanding of transcellular transport and its regulation has helped us appreciate the mechanisms of animal adaptation to fresh- and saltwater, it has led to the discovery of the molecular defect in cystic fibrosis, and it has aided the development of new drugs (diuretics). The mechanisms of transport between cells are just now beginning to receive attention. A major advance in this direction was made during the previous NSF award period in the laboratory of the PI: the first demonstration that an extracellular peptide (leucoknin, a neurohormone) regulates a transport pathway outside the cell. Whether this pathway is between cells, the so-called paracellular pathway, is the first and most important objective of the continuation of this work. The second objective is the detailed examination of the ion pump located in the cell membrane facing the urine side of the kidney. The third objective is to discover new hormones involved in the regulation of transport. This work is done in isolated kidneys of insects, the so-called Malpighian tubules of the yellow fever mosquito.