The adrenal medulla is involved in the control of cardiovascular functions, especially during stress reactions. Epinephrine and norepinephrine are the hormones by which it exerts these effects. This picture has changed drastically with the discovery of adrenomedullary peptide hormones, called enkephalins, that act like opiates when given via injections. The function(s) of these hormones, when released by the adrenal, are unknown though it has been speculated that they have euphoric and analgesic effects. However, being peptides, these enkephalins do not have access to several regions of the central nervous system (because of the presence of a blood-brain barrier). To make matters more confusing, it is now clear that even true opiates, codeine and morphine, are produced by the adrenal gland. These true opiates have access to many regions of the central nervous system. Obviously, an understanding of the interactions of these three different types of substances, which seem to be released simultaneously during stress, is of utmost importance for basic scientific and potentially therapeutic reasons. Unfortunately, mammals have rather low levels of circulating opiates, and are therefore only of limited value for pertinent research. However, the American eel is an ideal model for work on plasma opiates. Its adrenal medulla equivalent contains high concentrations of all three types of hormones, and it can be studied easily in vivo and in vitro. In addition, the plasma levels of codeine and morphine are several times higher than in mammals. Furthermore, the eel is much hardier under experimental conditions than warm-blooded animals, and its central nervous system is much easier to study than that of the latter. In this proposal the eel is employed because this species has unique features for research on the functions and interactions of the three types of secretions of the adrenal medulla. Experimental approaches include:(a) measurement of hormone release in vivo and in vitro; (b) analysis of the possible physiological effects of enkephalins and opiates on cardiac, respiratory, osmoregulatory, metabolic and endocrine functions, and on agonistic behavior. These studies should (1) help to clarify the functions of the chromaffin secretory cocktail, particularly during stress responses; (2) help to understand pathologies related to the chromaffin cell; and (3) provide basic insights for the understanding of the chromaffin cell system of the human embryo/fetus, which is similar to that of Anguilla rostrata.
