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曼氏血吸虫:血清素及血清素受体拮抗剂对体外初代子胞蚴运动性和长度的影响

Schistosoma mansoni: effects of serotonin and serotonin receptor antagonists on motility and length of primary sporocysts in vitro.

作者信息

Boyle J P, Zaide J V, Yoshino T P

机构信息

Department of Pathobiological Sciences, Biotron, University of Wisconsin-Madison, 53706, USA.

出版信息

Exp Parasitol. 2000 Apr;94(4):217-26. doi: 10.1006/expr.2000.4500.

Abstract

The effects of serotonin (5-hydroxytryptamine; 5-HT) on in vitro transformed primary sporocysts of Schistosoma mansoni were investigated. Serotonin treatment significantly increased parasite motility (percentage of motile sporocysts) and length at concentrations as low as 1 microM. These effects were mimicked by the 5-HT agonist tryptamine, albeit with 10- to 100-fold less potency. The effects of 10 microM 5-HT on sporocyst motility were observed within 15 min posttreatment and on parasite length by 6 h posttreatment, and both effects were stable for up to 48 h. Receptor antagonists with varying affinities for defined vertebrate neurotransmitter receptor subtypes were examined for their effects on parasite behavior in the absence and presence of 10 microM 5-HT. In the absence of 5-HT, only methiothepin significantly inhibited normal parasite growth after 48 h of incubation. In the presence of 10 microM 5-HT, the serotonin receptor antagonists mianserin, ketanserin (both at 100 microM), and methiothepin (at 10 microM) significantly inhibited 5-HT-induced lengthening of primary sporocysts, while 3-tropanyl-indole-3-carboxylate and chlorpromazine had no significant effect. The effects of these same drugs on parasite motility were also examined. In the absence of 5-HT, 10 microM chlorpromazine increased parasite motility, while the other antagonists had no effect. When sporocysts were treated with 10 microM 5-HT for 2 h in the continued presence of antagonist, 100 microM mianserin, ketanserin, 3-tropanyl-indole-3-carboxylate, and 10 microM methiothepin inhibited 5-HT induced increases in parasite motility, while 10 microM chlorpromazine had no effect. These results show that primary sporocysts of S. mansoni exhibit behavioral responses to serotonin much like adult stages of this parasite. Furthermore, these responses appear to be mediated via receptors with pharmacological similarities to those previously described in adult worms.

摘要

研究了血清素(5-羟色胺;5-HT)对曼氏血吸虫体外转化的原代子孢蚴的影响。血清素处理在低至1微摩尔的浓度下就能显著提高寄生虫的运动能力(活动子孢蚴的百分比)和长度。5-HT激动剂色胺能模拟这些作用,尽管效力要低10到100倍。10微摩尔5-HT对子孢蚴运动能力的影响在处理后15分钟内即可观察到,对寄生虫长度的影响在处理后6小时出现,且两种影响在长达48小时内都保持稳定。研究了对特定脊椎动物神经递质受体亚型具有不同亲和力的受体拮抗剂在不存在和存在10微摩尔5-HT的情况下对寄生虫行为的影响。在不存在5-HT的情况下,只有甲硫噻平在孵育48小时后能显著抑制正常寄生虫的生长。在存在10微摩尔5-HT的情况下,血清素受体拮抗剂米安色林、酮色林(均为100微摩尔)和甲硫噻平(10微摩尔)能显著抑制5-HT诱导的原代子孢蚴伸长,而3-托烷吲哚-3-羧酸酯和氯丙嗪则无显著影响。还研究了这些相同药物对寄生虫运动能力的影响。在不存在5-HT的情况下,10微摩尔氯丙嗪可提高寄生虫运动能力,而其他拮抗剂则无作用。当子孢蚴在拮抗剂持续存在的情况下用10微摩尔5-HT处理2小时时,100微摩尔米安色林、酮色林、3-托烷吲哚-3-羧酸酯和10微摩尔甲硫噻平可抑制5-HT诱导的寄生虫运动能力增加,而10微摩尔氯丙嗪则无作用。这些结果表明,曼氏血吸虫的原代子孢蚴对血清素表现出的行为反应与该寄生虫的成虫阶段非常相似。此外,这些反应似乎是通过与先前在成虫中描述的具有药理学相似性的受体介导的。

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