McGowan K, Guerina V, Wicks J, Donowitz M
Ciba Found Symp. 1985;112:139-54. doi: 10.1002/9780470720936.ch8.
Watery diarrhoea as distinct from dysentery is occasionally seen in intestinal amoebiasis, suggesting a component of intestinal secretion. To study the pathogenesis of this watery diarrhoea, we evaluated the effect of lysates of Entamoeba histolytica on active intestinal electrolyte transport using rabbit ileum and rat colon studied by the Ussing chamber-voltage clamp technique. Amoebic lysates added to the ileal and colonic mucosal surfaces did not alter electrolyte transport; in contrast, addition to the ideal and colonic serosal surfaces caused an increase in short-circuit current which was transient in the ileum but more prolonged in the colon. This increase in current corresponded to inhibition of active Na+ and Cl- absorption and apparent stimulation of Cl- secretion in rat colon. In rabbit ileum, the short-circuit current response was: (1) dependent on serosal Ca2+, (2) inhibited by serosally applied verapamil, (3) associated with reversible desensitization, and (4) only partially inhibited by heating. These characteristics were similar to those of a series of neurohumoral substances present in mammalian intestinal mucosa which affect active electrolyte transport by increasing the permeability of the basolateral membrane to Ca2+. Substances with these properties identified include serotonin, substance P and neurotensin. All three substances were shown to be present in amoebic lysates by radioimmunoassay. Serotonin was also present by high performance liquid chromatography (HPLC) and thin layer chromatography, and neurotensin by HPLC. Prostaglandins were not present by radioimmunoassay. Attempts were made to determine which of these neurohumoral substances contributed to the changes in intestinal transport caused by amoebic lysates. Serotonin was thought to be involved, from the inhibition of the transport effect of amoebic lysate on rat colon by anti-serotonin antibody and by bufotenine, which inhibits the effect of serotonin on ion transport. Prostaglandins also appeared to be involved, since pretreatment with PGE2 or indomethacin inhibited the effects of amoebic lysate on transport. We conclude that amoebae contain neurohumoral substances, including serotonin, neurotensin and substance P, which may be important in the intestinal secretion caused by amoebae. Serotonin appears partially responsible for the intestinal secretion. In addition, amoebae may induce prostaglandin synthesis by the intestinal mucosa which could also contribute to the secretory response. The relation between the neurohumoral substances which act by Ca2+ and the prostaglandins presumably caused to be synthesized in the intestinal mucosa is not known.
与痢疾不同的水样腹泻偶尔可见于肠道阿米巴病，提示存在肠道分泌成分。为研究这种水样腹泻的发病机制，我们使用Ussing室电压钳技术，通过兔回肠和大鼠结肠评估溶组织内阿米巴裂解物对肠道主动电解质转运的影响。添加到回肠和结肠黏膜表面的阿米巴裂解物未改变电解质转运；相反，添加到回肠和结肠浆膜表面会导致短路电流增加，这在回肠中是短暂的，但在结肠中持续时间更长。这种电流增加对应于大鼠结肠中主动Na⁺和Cl⁻吸收的抑制以及Cl⁻分泌的明显刺激。在兔回肠中，短路电流反应具有以下特点：（1）依赖于浆膜Ca²⁺；（2）受浆膜施加的维拉帕米抑制；（3）与可逆脱敏相关；（4）仅部分受加热抑制。这些特征与哺乳动物肠道黏膜中存在的一系列神经体液物质相似，这些物质通过增加基底外侧膜对Ca²⁺的通透性来影响主动电解质转运。已确定具有这些特性的物质包括5-羟色胺、P物质和神经降压素。通过放射免疫测定显示，这三种物质均存在于阿米巴裂解物中。通过高效液相色谱（HPLC）和薄层色谱也检测到5-羟色胺的存在，通过HPLC检测到神经降压素的存在。通过放射免疫测定未检测到前列腺素。我们试图确定这些神经体液物质中哪些导致了阿米巴裂解物引起的肠道转运变化。抗5-羟色胺抗体和蟾蜍色胺抑制5-羟色胺对离子转运的作用，从而使5-羟色胺被认为参与其中，蟾蜍色胺可抑制阿米巴裂解物对大鼠结肠的转运作用。前列腺素似乎也参与其中，因为用前列腺素E2或吲哚美辛预处理可抑制阿米巴裂解物对转运的影响。我们得出结论，阿米巴含有神经体液物质，包括5-羟色胺、神经降压素和P物质，它们可能在阿米巴引起的肠道分泌中起重要作用。5-羟色胺似乎部分负责肠道分泌。此外，阿米巴可能诱导肠道黏膜合成前列腺素，这也可能导致分泌反应。通过Ca²⁺起作用的神经体液物质与可能在肠道黏膜中合成的前列腺素之间的关系尚不清楚。
