U.S.- Austria Cooperative Research on the Evolution and Ontogeny of the Functions of Conjugated Catecholamines

该奖项将支持托马斯·杰斐逊医学院的August Epple博士和奥地利格拉茨大学的Sepp Porta博士在比较生理学方面的合作研究。该项目的目的是提高对循环儿茶酚胺偶联物功能的理解，并为这些偶联物的完全未知的个体发生和进化提供见解。最近，人们已经清楚地认识到，许多，也许是所有脊椎动物的心血管染色质细胞产生一种复杂的分泌“鸡尾酒”，其信使物质除了儿茶酚胺外，还包括多肽和真正的阿片类药物（可待因和吗啡）。这些分泌物之间的相互作用在很大程度上是未知的，它们是美国Epple博士实验室正在进行的研究的主题。这些相互作用的复杂性通过循环儿茶酚胺、葡萄糖醛酸盐和硫酸盐进一步增强，这些物质已经被Porta博士在奥地利的实验室研究了多年。传统上，这些缀合物被认为是注定要排泄的代谢物。然而，现在看来，至少有一部分缀合物1)由肾上腺髓质释放，2)作为信使物质起作用。拟议的项目将采用系统发生/个体发生的方法，并将调查三个物种，其染色质细胞系统代表肾上腺髓质进化的三个水平（七鳃鳗，鳗鱼和老鼠），以及鸡胚胎，其染色质细胞系统类似于七鳃鳗。这些调查将结合埃普尔博士实验室在低等脊椎动物和鸡胚胎方面的经验，以及波尔塔博士实验室在分析共轭儿茶酚胺方面的技术专长。预期的数据将为共轭血浆儿茶酚胺作为生理调节剂的发生、进化和功能提供新的基本见解。

This award will support cooperative research in comparative physiology between Dr. August Epple, Thomas Jefferson Medical College, and Dr. Sepp Porta, University of Graz, Austria. The objective of this project is to improve understanding of the function of circulating catecholamine conjugates, and provide insights into the completely unknown ontogeny and evolution of these conjugates. Recently it has become clear that the cardiovascular chromaffin cells of many, and perhaps all, vertebrates produce a complex secretory "cocktail", whose messenger substances include, in addition to catecholamines, peptides and true opiates (codeine and morphine). The interactions between these secretions are largely unknown, and they are the subject of ongoing research in Dr. Epple's laboratory in the US. The complexity of these interactions is further enhanced by circulating catecholamine glucuronides and sulfates, substances that have been studied for a number of years by Dr. Porta's laboratory in Austria. Traditionally, these conjugates have been considered metabolites destined for excretion. However, it now appears that at least some fraction of the conjugates 1) are released by the adrenal medulla, and 2) function as messenger substances. The proposed project will apply a phylogenetic/ontogenetic approach and will investigate three species, whose chromaffin cell systems represent three levels in the evolution of the adrenal medulla (lamprey, eel and rat), as well as the chicken embryo, whose chromaffin cell system resembles that of the lamprey. The investigations will combine the experience of Dr. Epple's lab with lower vertebrates and the chicken embryo, and the technical expertise of Dr. Porta's lab in the analysis of the conjugated catecholamines. The expected data should provide new basic insights into the ontogeny, evolution and function of conjugated plasma catecholamines as physiological regulators.