The proposed research in developmental pharmacology deals with the development of sensitivity to beta adrenergic agonists and the role of the sympathetic nervous system in this process. Most of the studies concern the development of the positive inotropic effect of these agents. Our unpublished observations show that the sensitivity of the chick myocardium to the inotropic effects of Ca ions and isoproterenol change during development. Since beta adrenergic receptors are intimately associated with the adenyl cyclase system, these changes may well result from alterations in adenyl cyclase and related systems and/or in Ca ions metabolism. We therefore propose to make developmental studies on (1) the pharmacologic characteristics of beta adrenergic receptors, (2) adenyl cyclase and related systems and (3) Ca ions metabolism. The role of the sympathetic nervous system in controlling these developmental processes will be assessed by selectively destroying the adrenergic nerve terminals by injecting 6- hydroxydopamine into the yolk sac of fertilized eggs. The development of sensitivity to beta receptor-mediated responses in the embryonic chick liver will be studied by examining the relationship between the membrane hyperpolarizing and cyclic 3'5'-adenosine monophosphate elevating effects of catecholamines.