Spatio-temporal Analysis Of Rat Intestinal Motility In Physiological And Disease Models
Funder
National Health and Medical Research Council
Funding Amount
$358,750.00
Summary
This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping ....This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping behaviour to prevent over-filling or to eject toxic or irritating substances (eg: some laxatives activate this mechanisms). This is often called peristalsis. A third mechanism consists of activity of nerve cells in the gut, that slowly propagates along the intestine and causes the muscle to contract, sweeping along any remnants. The movements generated by these three mechanisms occur in segments of intestine isolated from rats. The major difficulty up until now has been to relate the actual movements in living animals to these fundamental mechanisms. It is now possible to bridge this gap because we have developed methods to record, display and measure graphically the actual movements. Movements are transformed into spatio-temporal maps which show all of the contractions over a period of time. Coordinated activity is visible in these maps as recognisable patterns or visual objects. Measurements can be readily made with conventional statistics. The literature in gastroenterology is full of descriptions of motility based on indirect methods of recordings. In this project we will be able to correlate the previous indirect methods with the new graphic methods and thus establish a clearer, simpler and more accurate classification of normal patterns of intestinal motility. We will then use this to establish what goes wrong in a number of experimental diseases known to affect adversely the movements of the intestine.Read moreRead less
The Neural Control Of Serotonin Release From Intestinal Enterochromaffin (EC) Cells
Funder
National Health and Medical Research Council
Funding Amount
$117,187.00
Summary
Many functional gastrointestinal problems are believed to be caused by a disruption of the normal functioning of the nerves within the wall of the gut. These nerves are believed to receive information about the contents of the intestine from a specialised class of cell lining the inside wall of the gut called the enterochromaffin cell. The enterochromaffin cell does this job by modulating the release of the transmitter serotonin. In some disorders, like the Irritable Bowel Syndrome (IBS) which c ....Many functional gastrointestinal problems are believed to be caused by a disruption of the normal functioning of the nerves within the wall of the gut. These nerves are believed to receive information about the contents of the intestine from a specialised class of cell lining the inside wall of the gut called the enterochromaffin cell. The enterochromaffin cell does this job by modulating the release of the transmitter serotonin. In some disorders, like the Irritable Bowel Syndrome (IBS) which can affect the upper and lower intestine, the information that serotonin carries can become confused. Thus, the control of the release of serotonin from the enteroendocrine cell is an important process to understand in health and in disease. We will investigate this release directly in isolated tissues from guinea pig small and large intestine and from human large intestine. This study will examine the role of serotonin and the modulation of its release from the enterochromaffin cell. Problems with serotonin release may underlie disease, thus, understanding how this release is controlled will provide a foundation for new and specific therapies that target channels or receptors specific to the release of serotonin. These data could help to develop therapies for gastrointestinal problems such as the IBS, chronic intestinal pseudo-obstruction and gastro-oesophageal reflux disease. The release of serotonin is also intimately linked with the diarrhea associated with cholera and anti-cancer treatments. The proposed study will contribute to the ongoing development of specific therapies that block serotonin receptors on the nerve terminal and will lead to new therapies that compliment existing therapies by modulating the release of serotonin.Read moreRead less
The Knotty Problem Of Enterochromaffin Cells And Gastro-intestinal Function: Unravelling Cause And Effect
Funder
National Health and Medical Research Council
Funding Amount
$403,097.00
Summary
It is crucial to understand how the food we eat controls the secretions and movements of a healthy or a diseased gastrointestinal (GI) system. One way control is achieved involves the release of serotonin (5-HT) from the enterochromaffin cells present in the epithelial lining of the intestine. This is the subject of our proposal and our results will help us to understand the causes of GI disorders and help to formulate new treatments.
Mechanisms By Which Aging Induces Constipation In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$369,717.00
Summary
Chronic constipation is one of the most common reasons why the elderly community seek medical attention. There is now strong evidence to suggest that the high prevalence of constipation in the elderly is likely due to a dramatic loss of specific nerves that lie in the wall of the colon. This project will use latest imaging technologies to identify the mechanisms by which these nerves are impaired with age that lead to constipation in the elderly.
Effects Of Ischemia/ Reperfusion Injury On Enteric Neurons And Neuroprotective Strategies
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
The intestine can suffer restricted blood flow, creating a region of damaged or dead bowel. This leads to severe medical emergencies, complications and even death. Loss of blood flow and damage can be a serious complication for intestinal transplant surgery, which compromises patient survival and recovery. The project brings together transplant surgeons and basic scientists to solve problems caused by intestinal ischemia. A major result will be to improve outcomes for Australian patients
The Role Of Transferrin Receptor, Divalent Metal Transporter, Ferroportin And Hemochromatosis Protein In Iron Absorption
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been i ....Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been identified but how the defective protein causes the cells of the intestine to absorb more iron into the body than is needed remains unknown. This has led to the idea that the normal protein is responsible for controlling the amount of iron absorbed. Recent studies have shown a link between this protein and another called transferrin receptor. These two molecules are thought to co-operate in determining how much iron will be absorbed. Once this is determined other molecules called iron transporters are produced and these are responsible for moving the iron from the intestine into the blood. When not much iron is required only a small number of transporters are made and when more iron is required then many more are produced. How these transporters program the level of iron absorption is unknown but the process probably involves the transferrin receptor and the hemochromatosis protein. This project will investigate the function of the molecules that determine the programe for how much iron is to be absorbed, and secondly how this is linked to the production and movement of the transproters that co-ordinate this function.Read moreRead less