Metabolism of Circulating Hormones by the Fish Gill

除了众所周知的呼吸功能外，哺乳动物的肺在调节各种血浆激素方面起着重要作用，同时也是其他血源分子的高效生物过滤器。肺的解剖结构非常适合进行这些活动，1)整个血量首先通过肺，然后在其他器官之间进行划分，2)肺广泛的毛细血管网络为血浆分子和代谢活跃细胞之间的相互作用提供了一个非常大的表面。该实验室之前的工作表明，鱼的鳃具有与肺相同的解剖特征，随后的研究证实，鳃像哺乳动物的肺一样能够代谢循环激素，如血管紧张素和儿茶酚胺、肾上腺素和去甲肾上腺素。因此，呼吸器官对激素的调节在脊椎动物的进化中发展得非常早，并不是肺所独有的特征。拟议的研究将进一步描述鳃对各种重要心血管激素的代谢能力，包括血管紧张素、心房利钠肽、儿茶酚胺、血清素和该实验室最近发现的一种新型血管活性肽激素T60K。一种分离的灌注鳃技术已经发展到量化代谢和确定重要的酶的步骤。这些研究的结果将与完整鱼类的激素代谢进行比较，以进一步确定鳃在激素调节中的总体重要性。此外，将对鳃代谢外来化合物（如在污染环境中发现的化合物）的能力进行初步筛选。分离和培养支柱细胞，内皮细胞独特的鳃，也将进行允许细胞特异性代谢活动。这项研究的结果将对内分泌控制机制和血管内皮作为代谢器官的系统发育发展感兴趣的内分泌学家和生理学家具有重要意义。这些结果也很重要，因为它们为进一步研究鳃代谢有毒物质的能力提供了初步方向，有毒物质通过血液或环境输送到鳃。//

In addition to its well-known respiratory function the mammalian lung plays an important role in regulating a variety of plasma hormones and also serves as a highly efficient biological filter of other blood-born molecules. The anatomy of the lung is ideally suited to perform these activities, 1) the entire blood volume first passes through the lung before it is divided between the other organs, and 2) the extensive capillary network of the lungs provide a very large surface for interactions between plasma molecules and metabolically active cells. Previous work in this laboratory has shown that the fish gill has anatomical features identical to the lung and subsequent studies have confirmed that the gill, like the mammalian lung is able to metabolize circulating hormones such as angiotensin and the catecholamines, epinephrine and norepinephrine. Thus hormone regulation by respiratory organs developed very early in vertebrate evolution and is not a feature unique to the lung. The proposed research will further delineate the metabolic capabilities of the gill with respect to a variety of important cardiovascular hormones including angiotensin, atrial natriuretic peptides, catecholamines, serotonin and a novel vasoactive peptide hormone T60K that was recently found in this laboratory. An isolated perfused gill technique has been developed to quantify metabolism and identify the important enzymatic steps. Findings form these studies will be compared to hormone metabolism in intact fish to further identify the over-all importance of the gill in hormone regulation. In addition, preliminary screening will be done on the ability of the gill to metabolize foreign compounds such as those found in polluted environments. Isolation and culture of pillar cells, endothelial cells unique to the gill, will also be done to permit cell-specific metabolic activity. Results form this research will be important to endocrinologists and physiologists interested in endocrine control mechanisms and the phylogenetic development of the vascular endothelium as a metabolic organ. These results are also important because they provide the initial direction for further work on the ability of the gill to metabolize toxic substances, the latter delivered to the gill via the blood or the environment.//