Integrative Properites Of Intrinsic Sensory Neurons Of The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$211,681.00
Summary
For the neuronal control of the intestine to be appropriate to the constantly changing state of the organ, it is essential that there is feedback concerning, amongst other things, distension by its contents and its contractile state. These properties of the intestine are monitored by intrinsic sensory neurons, which are very special sensory cells, because they are embedded in the wall of the organ that they control. They have only very recently been identified, and thus surprisingly little is kn ....For the neuronal control of the intestine to be appropriate to the constantly changing state of the organ, it is essential that there is feedback concerning, amongst other things, distension by its contents and its contractile state. These properties of the intestine are monitored by intrinsic sensory neurons, which are very special sensory cells, because they are embedded in the wall of the organ that they control. They have only very recently been identified, and thus surprisingly little is known about how they perform their functions. It is clear, however, that they have special ways of integrating information about their environment, and the activities of other neurons, that are not shared by any other sensory neurons identified to the present time. Thus investigation of these neurons will provide information that is almost completely lacking about how the intestine performs its tasks. This information will be valuable in defining targets for development of therapeutic compounds and in analysing disorders of intestinal motility.Read moreRead less
Long Term Changes In Excitability Of Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$198,414.00
Summary
A large proportion of the community, about 20% at any one time, suffer from functional bowel disorders, the most common of which is the irritable bowel syndrome (IBS). The bowel in these patients appears normal; there are no overt changes in its appearance. However, the patients have discomfort, pain, abdominal bloating and altered bowel habits, which can include constipation and-or diarrhoea. There is general agreement that an alteration in the responsiveness of sensory neurons of the digestive ....A large proportion of the community, about 20% at any one time, suffer from functional bowel disorders, the most common of which is the irritable bowel syndrome (IBS). The bowel in these patients appears normal; there are no overt changes in its appearance. However, the patients have discomfort, pain, abdominal bloating and altered bowel habits, which can include constipation and-or diarrhoea. There is general agreement that an alteration in the responsiveness of sensory neurons of the digestive tract occurs in IBS. Until our recent discovery of long-term increases in excitability of intrinsic sensory neurons in the small intestine, no possible cellular basis for altered sensory neuron responsiveness that could underlie IBS had been found. We will investigate the mechanism of the long-term increase in excitability and will investigate drugs that are expected to modify its induction and-or maintenance. We expect that this work will aid in unravelling the genesis of IBS and will eventually lead to strategies to treat this common debilitating condition.Read moreRead less
Mechanisms Of Long Term Excitability Changes In Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$308,250.00
Summary
The intestine contains within its walls a nerve circuitry, the enteric nervous system, that controls many of its activities. The intestine itself adapts to circumstances, such as diet, and to pathological changes, such as infection or inflammation. In fact, changes in the intestine can outlast the events that cause them. This implies that there are prolonged changes in properties of control systems in the intestine. We have discovered that the intrinsic sensory neurons of the intestine exhibit l ....The intestine contains within its walls a nerve circuitry, the enteric nervous system, that controls many of its activities. The intestine itself adapts to circumstances, such as diet, and to pathological changes, such as infection or inflammation. In fact, changes in the intestine can outlast the events that cause them. This implies that there are prolonged changes in properties of control systems in the intestine. We have discovered that the intrinsic sensory neurons of the intestine exhibit long-term excitability increases following prolonged, low frequency, stimulation of their inputs from other neurons. This phenomenon has been called sustained slow postsynaptic excitation (SSPE). We have begun to examine the mechanisms behind the SSPE, and have discovered that it involves the enzymatic modification of molecules in the intrinsic sensory neurons. In this work, we will identify the enzymes and their molecular targets. This will add to basic knowledge of how the digestive system performs its task and adapts over time. It will provide data that can be used to predict molecules that might be of therapeutic value in dealing with chronic disorders in the intestine, such as irritable bowel syndrome.Read moreRead less
Roles Of The Peptide Hormone, Ghrelin, In The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$414,326.00
Summary
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Characterisation Of Ion Channels That Are Potential Therapeutic Targets In Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$535,141.00
Summary
Disorders of intestinal movement (motility) are common and cause considerable suffering, absenteeism and social disruption. Disorders include motility disturbances that occur in irritable bowel syndrome (IBS); constipation, which is a considerable problem in the aged; slow transit disorders; and diarrhoea. The movements of the intestine are controlled by the enteric nervous system. This project aims to find targets for therapy of motility disorders within the enteric nervous system