Giardia, a common enteric protozoan parasite is a well-recognized cause of diarrhoeal illness. The detailed mechanism of diarrhoea due to this infection is not well understood. A 58 kDa enterotoxin (ESP) was purified from the excretory–secretory product of the parasite. The present study was designed to investigate the mode of action of this enterotoxin of G. lamblia in mice enterocytes. An increase in cyclic adenosine monophosphate level, as well as intracellular Ca2+ concentration, was observed in the ESP-triggered enterocytes. The levels of phospholipase Cγ1 and inositol triphosphate were found to be upregulated. The activity of protein kinase C (PKC) in the enterocytes was also enhanced following stimulation with the ESP. An increase in the level of reactive oxygen species in ESP-stimulated cells correlated well with the decline in the activity of antioxidant enzymes (superoxide dismutase and catalase). The significantly high levels of nitrite and citrulline indicated the generation of reactive nitrogen intermediates in the ESP-triggered enterocytes. Thus, ESP could induce cross-talk among the different signal transduction pathways in the enterocytes, which could together bring about a common secretory response.

The mechanism by which Giardia lamblia exerts its pathogenicity is likely to be multifactorial. A 58 kDa enterotoxin was purified and characterized from the excretory–secretory product (ESP) of the parasite (Kaur et al. 2001). In the present study an attempt has been made to elucidate the mechanism of action of the ESP, a potentially important enterotoxin. A 41 kDa glycoprotein was identified in the mouse enterocyte membrane fraction with which the ESP interacted in a GM1-specific manner. The GTPase activity was reduced in enterocytes stimulated with the ESP, resulting in an increase in the level of adenylate cyclase-dependent cyclic adenosine monophosphate (cAMP). The activity of protein kinase A (PKA) in the enterocytes was also upregulated after ESP treatment. Ultimately, a significant increase in intracellular Ca2+ concentration and decrease in cytosolic Cl− level were noticed in ESP-stimulated mouse enterocytes. Thus it is possible that the enterotoxic ESP could bind to the 41 kDa glycoprotein (receptor?) on the enterocytes and activate the G-protein-mediated signal transduction pathway resulting in alteration of electrolyte transport.