The overall goal of this work is to determine the mechanisms of evolution of physiological regulatory systems. We have identified an excellent model system for such studies: the gastrointestinal hormones cholecystokinin (CCK) and gastrin in the alligator. We will test the hypothesis that gastrin and gastrin receptors evolved from CCK and CCK receptors in the primitive reptilia. The specific aims of the proposed studies are to determine the structures of CCK and gastrin in the alligator and to determine the properties of the alligator CCK and gastrin receptors. Alligators are important in evolutionary studies because they are closely related to the ancient reptiles that gave rise to all modern birds and mammals. including man. One of the hallmarks of evolution is the generation of new systems for regulation physiological processes, such as digestion. This increased sophistication of digestion played a major role in the evolution of endothermy, or warm-bloodedness, characteristic of birds and mammals. Endothermy, in turn, allowed birds and mammals to become much more successful than reptiles. Thus, studies of hormones and their responses in alligators will lead to important new insights into the mechanisms of evolution of physiological systems crucial to the success of life.