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.//