Motilin is a gastrointestinal hormone which may regulate intestinal motility. The precise molecular nature and tissue distribution of motilin, and mechanisms of motilin induced gut contractions are controversial due to use of antisera against porcine motilin and synthetic porcine motilin for studies in non- porcine species. Paucity of anatomical and physiological information on enteric nerves in the species studied is also a compounding problem. This study focuses on the synthesis, localization and function of the prepromotilin derived peptides, motilin and motilin associated peptide (MAP). Motilin cDNA from guinea pig gut will be used to detect prepromotilin mRNA by Northern analysis and in situ hybridization. Nucleotide sequence determination will permit synthesis of guinea pig motilin and MAP for use in studies on single enteric neurons in vitro and intestinal motility studies in vivo, as well for antisera generation to study motilin/MAP processing by RIA, HPLC and immunohistochemistry. Conducting these studies in guinea pigs, a species with a well characterized enteric nervous system, will make it possible to assign motilin/MAP actions to specific neuronal sub-populations with defined interactions and effector targets. Studying the biology of motilin/MAP from the level of gene expression to physiological action(s) in the intact animal should define their role in gastrointestinal function.
