A sexually dimorphic effect of cholera toxin: rapid changes in colonic motility mediated via a 5‐HT3 receptor‐dependent pathway in female C57Bl/6 mice

Gayathri K Balasuriya, Elisa L Hill-Yardin, Michael D Gershon, Joel C Bornstein

Extensive studies of the mechanisms responsible for the hypersecretion produced by cholera toxin (CT) have shown that this toxin produces a massive over-activation of enteric neural secretomotor circuits. The effects of CT on gastrointestinal motility, however, have not been adequately characterised. We investigated effects of luminal CT on neurally mediated motor activity in ex vivo male and female mouse full length colon preparations. We used video recording and spatiotemporal maps of contractile activity to quantify colonic migrating motor complexes (CMMCs) and resting colonic diameter. We compared effects of CT in female colon from wild type and mice lacking tryptophan hydroxylase (TPH1KO). We also compared CMMCs in colons of female mice in estrus with those in proestrus. In female (but not male) colon, CT rapidly, reversibly, and concentration-dependently, inhibits CMMC frequency and induces a tonic constriction. These effects were blocked by granisetron (5-HT3 antagonist) and were absent from TPH1KO females. CT effects were prominent at estrus but absent at proestrus. The number of EC cells containing immunohistochemically demonstrable serotonin (5-HT) was 30% greater in female mice during estrus than during proestrus or in males. We conclude that CT inhibits CMMCs via release of mucosal 5-HT, which activates an inhibitory pathway involving 5-HT3 receptors. This effect is sex- and estrus cycle-dependent and is probably due to an estrus cycle-dependent change in the number of 5-HT containing EC cells in the colonic mucosa. This article is protected by copyright. All rights reserved.