Receptor Mechanisms Laboratory
Research
Brief description of project/s
The laboratory is currently focused on investigating novel aspects of 3 distinct receptor systems.
- The long-standing interest in angiotensin receptor pharmacology remains a key focus of the laboratory. Antagonists of the AT1 receptor have become effective therapeutic agents in cardiovascular diseases. In collaboration with Carl Sciesser and James Angus we are investigating the potential of novel selenium containing angiotensin receptor antagonists to determine if they have an improved profile of activity in a range of cardiovascular diseases.
- Investigation of the growth promoting properties of angiotensin II stimulated collaboration with Professor Alastair Stewart on the properties of an orphan G-Protein coupled receptors GPR3. This protein had 20-30% sequence homology with GPCRs for a variety of chemoattractants and peptides including the high affinity IL8 receptor and the angiotensin II AT1 receptor, however none of the known peptide ligands for these receptors showed affinity for GPR30. We are investigating the possibility that GPR30 may play a role in tissue remodelling processes and may be involved in the non-genomic actions of oestrogens.
- In collaboration with Professor Peter McIntyre, we are investigating changes in the sensitivity and activation properties of the transient receptor potential (TRP) channels TRP channels are a super-family of cation selective ion channels that are involved in many sensory functions. We are focusing on the temperature-sensing TRP channels that are recognised top play an important role in pain sensation. We are interested in determining how specific post-translational modifications of the TRPV1 and TRPV4 channels modulates their structure and function.
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Key References
Tara E. Sutherland, Robin L. Anderson, Richard A. Hughes, Emile Altmann, Michael Schuliga, James Ziogas & Alastair G. Stewart. 2-Methoxyestradiol - a unique blend of activities generates a new class of anti-tumour/anti-inflammatory agents. Drug Discovery Today, (in press).
Stewart AG. Ziogas J. Molecular and cellular targets in tissue remodelling. [Editorial] Pulmonary Pharmacology & Therapeutics. 19(1):1-2, 2006.
Lew MJ & Ziogas J. The two-state model of antagonist-AT1 receptor interaction: an hypothesis defended but not tested. Biochemical Pharmacology. 67:397-399, 2004
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