Pharmacological and autoradiographical characterization of serotonin transporter-like activity in sporocysts of the human blood fluke, Schistosoma mansoni.
The present study focuses on the role of the biogenic monoamine serotonin (5-hydroxytryptamine) in the biology of sporocyst stages of the human blood fluke, Schistosoma mansoni, and its importance during obligate development within its snail host Biomphalaria glabrata. Based on previous work demonstrating that snails infected with S. mansoni have reduced levels of 5-hydroxytryptamine, we hypothesized that sporocysts actively transport this molecule from the host milieu. Intact sporocysts isolated in vitro take up exogenous 5-hydroxytryptamine via a high-affinity mechanism (K(m)=1.4 micromol l(-1)), and this serotonin transporter-like activity is dependent upon extracellular Na(+) and Cl(-) and is highly sensitive to previously characterized serotonin transporter inhibitors. Autoradiography suggests that transported [(3)H]5-hydroxytryptamine localizes within the body of the sporocyst, and in many cases is found in apical gland cells. Moreover, serotonin transporter-like activity is absent in free-swimming miracidia, the infective stage for the snail host, and the increase in larval serotonin transporter-like activity after miracidium-to-sporocyst transformation is accompanied by a corresponding decrease in steady-state levels of transcripts for tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis. Overall our data suggest that S. mansoni larvae express surface-exposed serotonin transporter-like molecules, and that the transition from free-living miracidium to parasitic mother sporocyst is characterized by an increased dependence upon exogenous 5-hydroxytryptamine.
Boyle
J P
JP
Department of Animal Health and Biomedical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 1656 Linden Drive West, Madison, WI 53706, USA.
Hillyer
J F
JF
Yoshino
T P
TP
D000818:Animals; D001345:Autoradiography; D001693:Biological Transport, Active / Q000502:physiology; D002713:Chlorine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006790:Host-Parasite Interactions / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D033661:Oocysts / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D012550:Schistosoma mansoni / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D012701:Serotonin / Q000378:metabolism / Q000493:pharmacokinetics*; D012908:Snails / Q000469:parasitology; D012964:Sodium / Q000494:pharmacology
D005473:Fluoxetine; D012701:Serotonin; D002713:Chlorine; D012964:Sodium; D007099:Imipramine