Hormonal Modulation Of Prostatic Growth And Contractility
Funder
National Health and Medical Research Council
Funding Amount
$324,237.00
Summary
With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine ....With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine those cells which can contract as these may be of critical importance in the urethral obstruction. We hypothesize that an enzyme called protein kinase C may be implicitly involved in both cell growth and contractile function and we will examine the role of protein kinase C with a view ultimately to develop drugs which may interfere with this process and therefore aid in non-surgical treatment of the condition.Read moreRead less
Molecular Mechanisms Of G Protein-Coupled Receptor Cross Talk
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
The normal function of all living cells depends on how they respond to the multitude of physical and chemical stimuli to which they are constantly exposed. The majority of chemical stimuli acting on cells do so not by directly entering the cell, but rather by acting on specific types of receiver proteins on the cell's surface called receptors. One important family of receptors transmit their message to the inside of the cell by coupling to yet another type of protein known as the G protein. Aber ....The normal function of all living cells depends on how they respond to the multitude of physical and chemical stimuli to which they are constantly exposed. The majority of chemical stimuli acting on cells do so not by directly entering the cell, but rather by acting on specific types of receiver proteins on the cell's surface called receptors. One important family of receptors transmit their message to the inside of the cell by coupling to yet another type of protein known as the G protein. Aberrations in the normal function of these G protein-coupled receptors have been implicated in a wide variety of disorders, such as schizophrenia, pain and dementia. To date, most therapeutic approaches to treating these disorders have targeted individual types of G protein-coupled receptors thought to play a role in each disease state, but this has met with mixed success. One of the reasons for this is that each disorder actually involves more than one type of G protein-coupled receptor communicating with other types in a complex way. Our current proposal specifically focuses on some of the newer mechanisms that have been suggested to play an important role in the communication between different types of G protein-coupled receptors located in the same type of cell. An understanding of how such receptor proteins can communicate with one another in this situation is absolutely vital in unravelling processes involved in the maintenance of health, abnormalities that lead to disease and in the development of more effective treatments.Read moreRead less
The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. It is extremely important to unravel how each of these components, the stimulating agent, the receptor and G protein, works in order to understand how the cells respond to various chemical signals. To make this process even more complex, it was recently shown that another newly discovered group of proteins called receptor activity modifying proteins (RAMPs) too play a critical role in some systems. Understanding what actually is the role of these new players, and how they team-up with the other components to elicit a specific response to a chemical stimulus, forms the basis of this proposal. Such knowledge is central to the unraveling of the processes involved in the maintenance of health, abnormalities that lead to disease, and in the development of new treatments.Read moreRead less
Alteration Of Glucose Metabolism By GPCR Activation
Funder
National Health and Medical Research Council
Funding Amount
$444,796.00
Summary
In type 2 diabetes the effect of insulin to stimulate glucose transport in fat cells and skeletal muscle is impaired so there is great interest in identifying insulin-independent mechanisms that increase glucose transport. Several G protein-coupled receptors (GPCRs) regulate glucose transport independently of insulin but the mechanisms involved in these effects are largely unknown. This project investigates how GPCRs regulate glucose homeostasis and will evaluate them as potential treatments.
The Pharmacology And Physiology Of GABA-C Receptors
Funder
National Health and Medical Research Council
Funding Amount
$481,980.00
Summary
GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alz ....GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alzheimer's disease and schizophrenia. GABA-A and GABA-C receptors are members of the ligand-gated ion channel super family in which the ion channel forms an intergral and central part of the receptor. In response to GABA, the channel opens and chloride ions flow through the channel. This causes an inhibitory action i.e. the cell reduces its rate of firing. This project aims to study GABA-C receptors by investigating what proteins make up the ion channel, by studying the actions of a range of chemicals that have specific effects at these receptors and by identifying amino acids that are important for normal channel function. New chemicals identified in our studies will provide leads for the design and development of new therapeutic agents acting on the brain.Read moreRead less
Understanding The Mechanisms Used By G-protein Coupled Receptors To Regulate Insulin-independent Glucose Transport
Funder
National Health and Medical Research Council
Funding Amount
$105,590.00
Summary
In type 2 diabetes, stimulation of glucose transport in fat cells and skeletal muscle by insulin is impaired. As a result there is great interest in identifying insulin-independent mechanisms that increase glucose transport. Several G-protein coupled receptors (GPCRs) regulate glucose transport independently of insulin but the mechanisms involved in these effects are largely unknown. This project investigates how GPCRs regulate glucose transport for potential as treatments.