Novel substance P receptors on autonomic and sensory neurons regulating the viscera

Funded Activity Summary

Potentially harmful stimulation of the skin or the internal organs activates sensory nerves that send signals to the brain. These events often are perceived as painful. One chemical messenger transmitting these signals first to the spinal cord, and then to the brain, is a neuropeptide called substance P. During many chronic inflammatory conditions, such as inflammation of the bowel, these signalling pathways are sensitised so that stimuli that previously were not painful now are perceived as painful. This sensitisation has several different causes. One contributing factor seems to be related to a change in the receptor molecules that recognise substance P. Last year we discovered a new type of receptor for substance P, that is prominent in the nerve pathways between the gut and the spinal cord. This novel receptor has important characteristics that are different from the classical substance P receptor. However, we are still largely ignorant about how substance P interacts with these new receptors to modify the activity of nerve cells in sensory pathways. Indeed, we propose that these new receptors are likely to make a significant contribution to the sensitisation that occurs in inflammation. We will use a combination of sophisticated cellular and molecular techniques to study the way in which substance P acts on these novel receptors in nerves regulating the visceral organs. Our results are likely to make a significant contribution to the development and interpretation of rational new therapies for treating chronic diseases of the gastrointestinal tract, such as inflammatory bowel disease (IBD). Our studies will reveal signalling mechanisms that also are likely to be used by substance P more widely in the nervous system, that are relevant to other inflammatory conditions like arthritis, and even some forms of depression.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $447,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical parasitology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

G-protein coupled receptors | gastrointestinal infections | inflammatory bowel disease | intracellular calcium | neurogenic inflammation | neuropathic pain | neuropeptides | neuropharmacology | tachykinin receptors

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