Physiological Function Of Nedd4-2 In Regulating The Epithelial Sodium Channel And Cystic Fibrosis Transmembrane Conductance Regulator
Funder
National Health and Medical Research Council
Funding Amount
$949,572.00
Summary
Optimal transport of sodium and chloride ions is essential for the maintenance of electrolyte balance, blood volume, blood pressure and lung function. We are studying the control of a key sodium channel (the epithelial sodium channel) and a key chloride channel (cystic fibrosis transmembrane conductance regulator) by an enzyme called Nedd4-2. This project will enable us to understand how Nedd4-2 regulates these two ion channels and to study the pathological consequences of the loss of Nedd4-2.
The Role Of Peroxisome Proliferator Activated Receptor Gamma In Sodium Transport In Human Proximal Tubule Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the de ....Renal failure accounts for a considerable component of the excess morbidity and mortality observed in patients with diabetes mellitus. In addition, the emotional, social and cost to the community of dialysis is enormous. PPARgamma is activated by drugs that have been recently introduced for the treatment of type 2 diabetes mellitus. The propensity for these drugs to cause fluid retention has emerged recently as the most common serious adverse drug reaction associated with these compounds. the definitive cause of fluid retention with the use of PPAR gamma agonists is not known. Studies reported in the last 12 - 18 months have suggested that a common pathway may be involved in the development of the fluid retention, the high blood pressure and the scarring that occurs in the kidney. This project will be the first to provide a comprehensive examination of the effect of PPARgamma induction on renal sodium absorption and fluid retention in the human proximal tubule cells and the potential molecular mechanisms underlying them. This will provide insight as to potential adjuvant treatments for patients with diabetes.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