SEROTONIN RECEPTORS: CHARACTERIZATION AND ONTOGEN

肠神经系统（ENS）是外周神经系统的一部分， 一种外部自主神经与一个更大的 提供神经支配的内在神经元及其过程的数量 到肠壁 ENS包含多种多样的假定或 建立神经递质。 个体发育机制控制 神经元表型表达是未知的。 为了深入了解 ENS中表型表达的调节， 特定的神经元特性，肠5-羟色胺受体（5-HTR），将被 研究了 5-羟色胺（5-HT），在神经控制中起作用， 胃肠蠕动，但其作用的细节不清楚 明白 5-HT刺激蠕动反射时，应用于 肠腔表面; 5-HT激活粘膜下神经节细胞， 在肌间神经丛的神经节中具有至少3种作用。 肠神经5-HTR最近已在兔中表征 使用放射性配体过滤结合研究和放射自显影;然而， 小鼠更适合研究ENS的发展，因为 (1)它们的小尺寸和相对低的成本便于实验和（2） 突变体和近交系是可获得的。 因此， 定义小鼠肠道中的肠道5-HTR。 初步研究表明， 小鼠具有5-HTR，并且事实上具有比兔子更高的5-HTR密度。 一旦成熟鼠5-HTR的性质已经通过 用分离的膜进行放射性配体测定，受体的个体发育 将进行放射自显影研究，并与其他事件进行比较， 肠道中的神经个体发育 5-羟色胺能神经元发育相当早， 个体发育 由于这些神经元在发育过程中与成神经细胞共存， 它们可以影响后期发育的神经元的表型表达。 了解肠道个体发育过程中5-HTR的时间和位置， 因此，这对检验5-HT在以下假设中发挥作用至关重要： 调节肠神经元发育。 在这些研究中获得的数据 将用于设计实验，以评估5-HTR在 利用新开发的肠神经特异性拮抗剂进行个体发育 5-HTR。 肠道神经肌肉发育有许多常见缺陷 这会导致大量的围产期发病率，手术，和一些 mortality. 更好地理解神经元的可能机制 表型表达可能有助于阐明这些病症的原因。

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.