The beta adrenergic receptors (betaAR) comprise one of the most studied families of G protein coupled receptors (GPCRs), and beta agonists and antagonists are commonly used in clinical pharmacology. Despite this cornucopia of scientific knowledge and clinical experience, comparatively little is know about betaARs and pain. The literature suggests contrasting views on the role of betaARs in pain. In some experimental conditions the activation of the receptor is pronociceptive and under other conditions it is anti-nociceptive leaving the role of the betaARs in pain uncertain. The mechanism of action of the effects of the betaARs on peripheral nociceptors have yet to be fully characterized and this represents an important gap in knowledge. In this application, we propose to test the central hypothesis that beta1 adrenergic receptor activation inhibits trigeminal nociceptors via a direct mechanism of action. Our preliminary results indicate that the mRNA encoding the beta1AR and identified beta1 receptor binding sites are present at greater levels in trigeminal ganglia (TGG) neurons than the beta2 receptor. In addition, application of a beta1 agonist inhibits release of iCGRP when stimulated with BK/PGE2. These preliminary data are consistent with the hypothesis that betaARs agonists inhibit nociceptors via activation of a beta1 adrenergic receptor mechanism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DE017307-03
Application #
7258875
Study Section
Special Emphasis Panel (ZRG1-F02B (20))
Program Officer
Hardwick, Kevin S
Project Start
2005-08-01
Project End
2008-05-31
Budget Start
2007-08-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$34,310
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Pharmacology
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Patwardhan, A M; Vela, J; Farugia, J et al. (2008) Trigeminal nociceptors express prostaglandin receptors. J Dent Res 87:262-6