Recent advances in genomics and proteomics techniques have allowed the interrogation of the genome/proteome to identify novel mechanisms underlying disease etiology. Ultimately such interrogations would encompass the complete chemical space of the cell, including endogenous small molecules or metabolome. An example that illustrates these challenges is the regulation of nociception. Conditions such as inflammation are known to sensitize our sense of touch and temperature such that non-noxious conditions become painful (allodynia) and noxious conditions become more painful (hyperalgesia). A prominent mechanism proposed to mediate this sensitization is the release of inflammatory mediators at the site of inflammation. This so- called inflammatory soup contains both proteinous as well as small molecular chemicals that are thought to sensitize ion channels expressed on nociceptive sensory neurons. Several ion channels of the transient receptor potential (TRP) family are known to function as sensors for temperature and a variety of structurally diverse chemicals that include pungent plant products such as capsaicin and mustard oil. Surprisingly however, only few endogenous ligands are known to date. The goal of this proposal is to establish an unbiased metabolome-wide approach for the identification of endogenous channel and receptor agonists.

Public Health Relevance

The goal of this proposal is to establish an unbiased metabolome-wide approach for the identification of endogenous activators of thermoTRPs involved in pain sensation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE021181-01
Application #
7961117
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Kusiak, John W
Project Start
2010-07-15
Project End
2012-06-30
Budget Start
2010-07-15
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$284,850
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Miyamoto, Takashi; Petrus, Matt J; Dubin, Adrienne E et al. (2011) TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin. Nat Commun 2:369