Potential Roles Of 5-hydroxytryptamine In Diseases Affecting The Colon
Funder
National Health and Medical Research Council
Funding Amount
$346,018.00
Summary
The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and ....The overall aim of this project is to examine the biological roles played by 5-hydroxytryptamine (5-HT) in the human colon. 5-HT is a naturally occurring substance of the body, normally involved in controlling many body activities. Relevance is placed in this project on the possibility that 5-HT is involved in causing or contributing to certain clinical conditions, either by excess or deficiency. The conditions that are the focus of this project are chronic constipation, diverticular disease and irritable bowel syndrome. It is a matter of concern that there are no specific treatments for these conditions to date, hence the thrust of the project is to increase knowledge in this area, so hopefully treatments will be developed. Our Pharmacology research group is recognised for its experience in defining drug effects on the intestine and in characterising the target sites on which they act. This has been achieved by using an integrated approach whereby different functional methods reliably detect effects at the levels of the muscle layers, the nerves that supply them and at the absorptive surface using experimental animals. In addition, the use of isolated pieces of human colon obtained from discarded operation material has been an invaluable inclusion into this process. This has allowed us to establish that 5-HT has a target site in the muscle of the colon and that this leads to relaxation and inhibition of the normal spontaneous contractile activity, said anecdotally to be abnormally high in patients with irritable bowel syndrome. We now wish to apply this expertise and knowledge to test whether 5-HT is involved in causing chronic constipation and diverticular disease and to design a drug that would be expected to be of value in treating patients with irritable bowel syndrome.Read moreRead less
Analysis Of Intracellular Signalling And Biological Activities Of The GM-CSF Receptor Family Using Constitutive Mutants
Funder
National Health and Medical Research Council
Funding Amount
$505,699.00
Summary
The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of th ....The cytokines GM-CSF, IL-3 and IL-5 stimulate the growth and actions of a wide range of blood cells. Each binds to a receptor on the cell surface which then triggers the generation of a number of signals inside the cell; it is these signals that are responsible for the cytokine?s actions. We have previously generated a panel of constitutive mutant forms of the beta subunit which is shared by the GM-CSF, IL-3 and IL-5 receptors. These constitutive mutants trigger signals even in the absence of the cytokine; importantly, the different mutants appear to trigger only a subset of the signals generated by the normal receptor. The aim of this project is to use our panel of constitutive beta subunit mutants to determine how the GM-CSF, IL-3 and IL-5 receptors generate signals inside the cell and how these signals lead to the various biological actions of the receptors on blood cell growth and maturation. Findings from this research will be relevant to the understanding and treatment of diseases which involve abnormal growth or function of blood cells such as leukaemia and inflammatory diseases.Read moreRead less