The enteric nervous system (ENS) is that part of the peripheral nervous system in which extrinsic autonomic nerves interact with a much larger number of intrinsic neurons and their processes to provide an innervation to the gut wall. The ENS contains a great diversity of putative or established neurotransmitters. The ontogenetic mechanisms controlling neuronal phenotypic expression are unknown. In order to gain insight into the regulation of phenotypic expression in the ENS, the development of a specific neuronal property, the enteric serotonin receptor (5-HTR), will be studied. Serotonin (5-HT), plays a role in the neural control of gastrointestinal motility but the details of its action are not well understood. 5-HT stimulates the peristaltic reflex when applied to the luminal surface of the gut; 5-HT activates submucosal ganglion cells, and has at least 3 actions in ganglia of the myenteric plexus. The enteric neural 5-HTR has recently been characterized in the rabbit using radioligand filtration binding studies and radioautography; however, mice are more suitable for studies of the development of the ENS because (1) their small size and relatively low cost facilitate experiments and (2) mutants and inbred strains are available. It is, therefore, important to define enteric 5-HTR in the mouse gut. Preliminary studies indicate that mice have 5-HTR and, in fact, have a higher 5-HTR density than rabbits. Once the properties of the mature murine 5-HTR have been established by radioligand assay with isolated membranes, the ontogeny of the receptors will be studied radioautographically and compared with other events of neuro-ontogeny in the gut. Serotonergic neurons develop quite early in ontogeny. Since these neurons coexist during development with neuroblasts, they could affect phenotypic expression by later developing neurons. Knowledge of the timing and location of 5-HTR during enteric ontogeny is thus critical to a test of the hypothesis that 5-HT plays a role in regulating enteric neuronal development. The data gained in these studies will be used to design experiments that will evaluate the role of 5-HTR in ontogeny by using a newly-developed specific antagonist of enteric neural 5-HTR. There are many common defects of enteric neuromuscular development that cause a great deal of perinatal morbidity, surgery, and some mortality. A better understanding of the possible mechanisms of neuronal phenotypic expression may help to clarify the cause of these conditions.
