REGULATION OF PHARYNGEAL PUMPING IN PARASITIC NEMATODES

丝虫、钩虫和各种肠道线虫感染全球数十亿人，而家养动物和栽培植物的线虫寄生虫对当今使用的抗线虫药物具有数十亿美元的影响，线虫化疗的未来方向是不确定的。显然，新的收缩是所有线虫的基本过程和5-羟色胺（5-HT）受体在两者的调节中起着关键作用，本研究旨在鉴定和表征寄生线虫猪蛔虫（Ascaris suum）的5-HT受体。具体地说，来自咽部和体壁肌肉的推定5-HT受体将使用RT-PCR用针对来自其他生物体的5-HT受体的保守区域设计的简并寡核苷酸和从分离自A的poly A+RNA制备的cDNA库来鉴定。咽肌和体壁肌。然后，将5-HT受体，特别是最近发现的5-HT 2-like受体亚型，在哺乳动物细胞系中进行功能性表达，并在生理制剂中研究腺苷酸环化酶活性、磷酸肌醇转换和咽泵的药理学和壁肌与5-HT依赖性变化的偶联。suum咽或体壁肌肉。这些研究应产生一个明确的描述5-HT受体在调节咽泵和肌肉收缩/代谢线虫的作用，并应提供一个很好的框架，这些基本过程的特异性抑制剂的发展。

Filarids, hookworms and a variety of intestinal nematodes infect billions of individuals worldwide, while nematode parasites of domesticated animals and cultivated plants have a multibillion dollar impact on the anti-nematodal drug in use today the future direction of nematode chemotherapy is uncertain. Clearly, new contraction are essential processes in all nematodes and serotonin (5-HT) receptors play a key role in the regulation of both, the present study was designed to identify and characterize 5-HT receptors in the parasitic nematode Ascaris suum. Specifically, putative 5-HT receptors from pharynx and body wall muscle will be identified using RT-PCR with degenerate oligonucleotides designed against conserved regions of 5-HT receptors from other organisms and cDNA pools prepared from poly A+RNA isolated from A. suum pharynx and body wall muscle. Then, the putative 5-HT receptors, especially the recently identified 5-HT2-like receptor isoforms, will be functionally expressed in mammalian cell lines and the pharmacology and coupling of the wall muscle and 5-HT dependent changes in adenyl cyclase activity, phosphoinositide turnover and pharyngeal pumping in physiological preparations of A. suum pharynx or body wall muscle. These studies should generate a clear description of the role of 5-HT receptors in the regulation of pharyngeal pumping and muscle contraction/metabolism in nematodes and should provide an excellent framework for the development of specific inhibitors of these essential processes.