Physiology - Theses
Permanent URI for this collection
Search Results
1 - 1 of 1
-
ItemSexual dimorphic effect of Cholera Toxin on colonic motility( 2015)Diarrhea is a combination of hypersecretion and increased gut motility. Bacterial toxins such as cholera toxin (CT) are a main cause of diarrhea around the world creating life threatening outbreaks. Although the effect of CT on hypersecretion is widely studied, its effect on motility remains largely unexplored. At the same time incidence of diarrhea, constipation and other GI tract related issues appear to be more frequent among females compared to men. GI complications are often reported with fluctuations in sex steroid hormone levels, such as pregnancy, menopause and the different stages of the menstrual cycle, indicating a direct relationship between sex hormones and functioning of the gastrointestinal tract. Therefore the main aim of this project was to evaluate the effect of CT on intestinal motility using both female and male C57Bl/6 mice. My results indicate that there is a sexually dimorphic and estrus cycle dependent effect of CT in C57Bl/6 mice. This CT induced reduction in the number of colonic migrating motor complexes is dependent on mucosal 5-HT acting on 5-HT3 receptors. I found increased nuclear labelling of Estrogen Receptor (ER) alpha in estrus females, which is an indication of increased genomic effects occurring during estrus. Therefore, I suggest the CT induced motility changes seen during estrus are due to the genomic effects of estrogens acting via ER alpha. I also identified increased expression of 5-HT containing EC cells and mast cells during estrus consistent with a large amount of literature suggesting that genomic regulation of estrogens produces increased 5-HT activity. NOS expression in the myenteric neurons and blockade of NOS with NOLA also showed a marked difference from estrus to proestrus, both approaches indicated increased NOS activity during estrus. In the light of the literature and my findings, I suggest the increased NOS activity seen during estrus is due to genomic effects of estrogens. Therefore, I conclude that the increased expression of 5-HT acting on 5-HT3 receptors and increased NOS activity due to genomic effects of estrogen are likely to be responsible for the motility changes observed during estrus on exposure to CT.