SEROTONIN RECEPTORS: CHARACTERIZATION AND ONTOGEN

肠神经系统(ENS)是周围神经一部分 外部自主神经与更大的 提供神经支配的内源性神经元及其突起的数量 直击肠壁。ENS包含大量不同的推定或 已建立的神经递质。个体发育调控机制研究进展 神经元的表型表达尚不清楚。为了深入了解 ENS中表型表达的调节，一种 特定的神经元特性，肠道5-羟色胺受体(5-HTR)，将是 学习。5-羟色胺(5-羟色胺，5-羟色胺)，在神经控制中发挥作用。 胃肠运动，但其作用的细节不是很好 明白了。5-羟色胺应用于脑组织时可刺激蠕动反射。 肠腔表面；5-羟色胺激活粘膜下神经节细胞； 在肌间神经丛的神经节内至少有3次活动。 肠神经5-HTR是最近在兔身上发现的 使用放射性配基过滤结合研究和放射自显影；然而， 小鼠更适合于研究神经内窥镜的发育，因为 (1)体积小，成本相对较低，便于实验和(2) 有突变体和近交系菌株可用。因此，重要的是， 在小鼠肠道中定义肠源性5-HTR。初步研究表明， 老鼠有5-HTR，事实上，比兔子有更高的5-HTR密度。 一旦建立了成熟的小鼠5-HTR的特性 离体膜放射配基分析--受体的个体发育 将通过放射自显影进行研究，并与其他事件进行比较 肠道中的神经个体发育。5-羟色胺能神经元在早期发育 个体发育学。由于这些神经元在发育过程中与神经母细胞共存， 它们可能通过以后发育的神经元来影响表型表达。 5-HTR在肠道个体发育中的时机和位置的知识是 因此对检验5-羟色胺在脑内的作用的假说至关重要 调节肠神经发育。从这些研究中获得的数据 将用于设计实验，以评估5-HTR在 新研制的肠神经特异性拮抗剂在个体发育中的作用 5-HTR。肠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，外科手术，以及一些 死亡率。更好地了解神经元的可能机制 表型表达可能有助于阐明这些疾病的原因。

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.