Neuropeptides and biogenic amines are important regulators of neuronal and muscular activity in both vertebrates and invertebrates (Snyder, 1980; Haynes, 1980). The recent discovery and characterization of a variety of neuropeptides has contributed significantly to our understanding of many diverse physiological functions. Furthermore, several studies indicate that the modulatory actions of some peptides and amines represent a novel form of neuronal communication (Woodward et al., 1979; Barker and Smith, 1980). The close association of amine and peptide pathways in the vertebrate brain (Hokfelt et al., 1980) and the existence of both putative transmitters in the same nerve terminals (Hokfelt et al., 1980; Pelletier et al., 1981; Potter et al., 1981) suggest that they are released together and interact at the target tissue. The widespread importance of these two classes of modulatory agents, their unique mechanisms of action, and close association with each other warrant further investigation into ther actions at the cellular and molecular level. Our research program incorporates the best aspects of invertebrate systems and mammalian neurochemistry and physiology. In many of the experiments outlined in this proposal we will use the neurogenic Limulus (horseshoe crab) heart to determine how proctolin (a pentapeptide) and several amines modulate neural networks and cardiac muscle. In addition, the heart will be used as a bioassay system to separate and purify Limulus neuropeptides, like proctolin, which will subsequently be tested for activity on vertebrate preparations. Antibodies to these peptides will be used to screen the vertebrate nervous system for related peptides. This approach has already led to the recent discovery of several novel peptidergic systems in the vertebrate brain (Weber et al., 1981; Dockray et al., 1981; Bodenmuller and Schaller, 1981), and we feel it makes the best use of both vertebrate and invertebrate preparations to develop and test concepts that are central to our understanding of peptidergic/aminergic systems in general.