inositol-1-4-5-trisphosphate and Diarrhea

By the use of a mouse model, the enteropathic effects of the simian immunodeficiency virus (SIV) surface unit (SU) envelope glycoprotein were explored. Purified SU (0.01-0.45 nmol) was administered intraperitoneally to 6- to 8-day-old mouse pups and induced a dose-dependent diarrheal response. Surgical introduction of SU into adult mouse intestinal loops revealed fluid accumulation without histological alterations and SU-treated unstripped intestinal mucosa induced chloride (Cl(-)) secretory currents in Ussing chambers. Similarly to rotavirus NSP4, the first described viral enterotoxin, SU induced a transient increase in intracellular calcium levels and increased inositol 1,4,5-triphosphate (IP(3)) levels in HT-29 cells. These data indicate the calcium response is mediated by IP(3). The presence of diarrhea and fluid accumulation within intestinal loops in the absence of histological alterations and induction of Cl(-) secretory currents demonstrate that SIV contains an enterotoxic domain localized within SU and is the second viral enterotoxin described.

Topics: Animals; Animals, Suckling; Calcium; Cell Line; Chlorides; Diarrhea; Dose-Response Relationship, Drug; Enterotoxins; Glycoproteins; HT29 Cells; Humans; Inositol 1,4,5-Trisphosphate; Intestinal Mucosa; Intestines; Mice; Mice, Inbred BALB C; Simian Immunodeficiency Virus; Viral Envelope Proteins

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia-infected mice in the presence or absence of dantrolene (1-(5(p-nitrophenyl)furfurilidene-amino) hydantoin sodium hydrate). There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of dantrolene resulted in significant net increase in absorption of Na+ and Cl- in control and experimental groups. Further, mouse intestinal epithelial cells were labelled with [32P]Pi and then treated with G. lamblia trophozoites and their excretory secretory products separately. The optimum time for inositol triphosphate formation was 15 min in control enterocytes as well as in treated enterocytes. A plateau was formed at higher concentrations. Since raised inositol triphosphate levels mobilize Ca2+ from intracellular stores and dantrolene traps Ca2+ within intracellular calcium stores, the present study thus suggests that intracellular calcium stores are involved in G. lamblia-induced diarrhoea in mice.

Topics: Animals; Biological Transport; Calcium; Chlorides; Dantrolene; Diarrhea; Giardia lamblia; Giardiasis; Inositol 1,4,5-Trisphosphate; Mice; Sodium

Topics: Calcium; Colon; Diarrhea; Epithelium; Humans; Inositol 1,4,5-Trisphosphate; Taurodeoxycholic Acid