Serotonin and intramolluscan stages of the human blood fluke, Schistosoma mansoni: Uptake, behavioral effects, and role in development.

摘要

Members of the genus Schistosoma are responsible for over 200 million cases of schistosomiasis, or bilharzia, in 76 countries worldwide, and continue to be a widespread public health problem despite numerous control efforts. Schistosomes are digenetic trematodes belonging to the phylum Platyhelminthes, and undergo obligatory development in a suitable snail host prior to becoming infective to humans. In our laboratory we are interested in interactions between larval, or sporocyst, stages of the causative agent of human intestinal schistosomiasis, S. mansoni, and the intermediate snail host Biomphalaria glabrata. Based on previous work suggesting an important role for 5-HT in sporocyst development, the effects of this compound on parasite physiology and behavior were examined. Exposure of whole S. mansoni sporocysts to 5-HT resulted in marked increases in muscle contractility, and these responses were dependent on 5-HT receptor activation. Moreover, whole sporocysts exhibited high-affinity (Km = ∼1.4 μM) 5-HT uptake, and this activity bore functional (ion dependence) and pharmacological (sensitivity to antidepressants) properties of SERTs characterized in other species. These data suggest that sporocysts may transport, and store, exogenously acquired (e.g., host) 5-HT, and that this process may not be necessary for 5-HT-induced motility changes. To directly test the dependence of 5-HT-induced motility changes on 5-HT uptake, sporocysts were treated with exogenous 5-HT in the presence of potent 5-HT uptake inhibitors, and contractile responses were assessed. In the complete absence of 5-HT uptake activity (e.g., in the presence of fluoxetine, or Prozac®), sporocyst motility responses were not inhibited, providing evidence that 5-HT uptake is not necessary for responses to exogenous 5-HT to occur, as we had originally hypothesized. The results of this work lead us to propose a model for the sporocyst tegument as both a 5-HT absorbtive and 5-HT responsive surface, and hypothesize that the acquisition of host 5-HT may be important for the intramolluscan development of larval stages of S. mansoni.