REGULATION OF PHARYNGEAL PUMPING IN PARASITIC NEMATODES

丝虫、钩虫和各种肠道线虫感染着全球数十亿人，而家养动物和栽培植物中的线虫寄生虫对当今使用的抗线虫药物产生了数十亿美元的影响线虫化疗的未来方向尚不确定。显然，新的收缩是所有线虫的基本过程，而5-羟色胺(5-HT)受体在两者的调节中起着关键作用，本研究旨在鉴定和鉴定寄生线虫猪蛔虫中的5-HT受体。具体地说，从咽部和体壁肌肉分离得到的5-羟色胺受体将通过RT-PCR和针对其他生物5-羟色胺受体保守区设计的简并寡核苷酸以及从猪咽和体壁肌肉中分离的Poly A+RNA制备的cDNA池来鉴定。然后，推测的5-羟色胺受体，特别是最近发现的5-HT2样受体亚型，将在哺乳动物细胞系和壁肌的药理和偶联中表达，并在猪咽或体壁肌肉的生理制剂中依赖于5-羟色胺对腺苷环化酶活性、磷脂酰肌醇周转和咽泵的影响。这些研究应该清楚地描述5-羟色胺受体在线虫咽泵和肌肉收缩/代谢调节中的作用，并为开发这些重要过程的特定抑制剂提供一个很好的框架。

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.