Neurogenic Diarrhoea: Lessons From Cholera Toxin And Related Bacterial Exotoxins
Funder
National Health and Medical Research Council
Funding Amount
$543,818.00
Summary
Many bacteria that cause diarrhoea act via the gut’s own nervous system to massively increase the transport of water and salt into the lumen of the intestine. In this project we will investigate mechanisms that lead to this over-excitation of the gut’s nervous system to test the idea that this is due to a change in the properties of the final nerve cells in the normal pathway that controls water transport. This will identify novel sites for drug treatments of diarrhoea.
Neural Coordination Of Intestinal Motility And Mucosal Secretion Of Water And Salt - Role In Toxin Induced Diarrhoea
Funder
National Health and Medical Research Council
Funding Amount
$490,020.00
Summary
This project deals with some of the basic mechanisms underlying disorders of gastrointestinal function and in particular with the mechanisms responsible for diarrhoea. Whenever there is a natural disaster (the recent tsunami for example) or a war, the breakdown of medical services leads to concern about outbreaks of cholera and other diarrhoea causing diseases, so understanding the mechanisms by which the cholera bacterium cause diarrhoea remains a major imperative. It is known that the diarrhoe ....This project deals with some of the basic mechanisms underlying disorders of gastrointestinal function and in particular with the mechanisms responsible for diarrhoea. Whenever there is a natural disaster (the recent tsunami for example) or a war, the breakdown of medical services leads to concern about outbreaks of cholera and other diarrhoea causing diseases, so understanding the mechanisms by which the cholera bacterium cause diarrhoea remains a major imperative. It is known that the diarrhoea resulting from cholera infection is produced by an enterotoxin, which acts to produce a massive over-secretion of water and salt through the intestinal wall, which if it is not controlled causes death by dehydration. This effect requires the activity of the nerve cells within the gut wall, the enteric nervous system (ENS). Other bacterial toxins have similar effects and also require activity of the ENS for these effects to be manifested. This project will identify how these toxins alter the activity of the ENS and the effects that they have on intestinal movements which are also regulated by the ENS. We already know that the movements and secretion of water are related to each other and that this relationship is disturbed in some more subtle diseases like irritable bowel syndrome. This project will characterise this relationship, thereby shedding light on the physiology underlying a variety of gastrointestinal disorders.Read moreRead less
Currents That Set The Excitability Of Enteric Neurons And Their Roles At Cell And Organ Levels
Funder
National Health and Medical Research Council
Funding Amount
$459,014.00
Summary
The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The refl ....The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The reflexes in the intestine that control its movements and secretion depend for their initiation on a special type of neuron, known as the intrinsic primary afferent neuron. These neurons have properties that determine how active they are. These properties distinguish them from all other enteric neurons. If the activity of intrinsic primary afferent neurons is controlled, then the intensity and character of enteric reflexes are also controlled. Thus it is feasible to target molecules in these neurons that could be used to treat constipation or diarrhoea, or to accelerate movement of food along the intestine. Our work has identified molecular targets and some of the medicinal compounds that could be useful to patients. The project will further define the molecular targets, determine the specificity of potential treatments and test the effectiveness of the medicinal compounds in an animal model.Read moreRead less