The objective of our research is to determine the role of neuropeptides in the regulation of neuroendocrine secretion and smooth muscle activity in the gut. Initial work on a prototypical neuropeptide, VIP, will now be extended to the major neuropeptides of the myenteric and submucosal plexuses: somatostatin, CCK-OP, methionine- and leucine-enkephalin, substance P and bombesin. Smooth muscle cells will be isolated from the longitudinal and circular smooth muscle of the intestine of the guinea pig and examined for the presence of specific receptors to neuropeptides. Receptors will be characterized in terms of mechnical activity, messenger systems (Ca++ fluxes and cAMP accumulation) and binding sites (radioiodinated ligands). The release of neuropeptides will be examined in muscle strips, vascularly perfused intestine and in isolated segments of fresh and cultured neural plexus. The regulation of an endocrine peptide (gastrin) by a paracrine peptide (somatostatin) and by cholinergic and peptidergic intramural neurons will be investigated in the vascularly perfused stomach of the rat.