The identification of opiate-like substances in extracts of the gastrointestinal tract and nervous system of vertebrates suggests that the known endogenous opiate-like peptides [Met5]- and [Leu5]-enkephalin might have a role in neurotransmission. In this study the gastrointestinal tract of guinea-pigs, rats and hamsters was examined by the immunoperoxidase-bridge method using specific antisera raised against [Met5]- and [Leu5]-enkephalin. Immunostained nerve fibers were most numerous in Meissner's plexus of the duodenum and in the circular muscle layer of the stomach and rectum of the guinea-pig. Nerve fibers in the guinea-pig esophagus and cardia of the stomach stained with [Met5]- but not with [Leu5]-enkephalin antiserum. Staining was not observed in any epithelial cells. The regional distribution of these peptides was also examined by radioimmunoassay of extracts of the gut of guinea-pigs and rats. The highest concentrations of [Met5]- and [Leu5]-enkephalin were found in extracts of guinea-pig duodenum at a ratio of 11:1, respectively. These findings provide evidence for an enkephalinergic nervous system in the gastrointestinal tract.
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