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.
