Project Details
Projekt
Involvement of P2 receptors in the modulation of nociceptive afferent stimuli
Applicants
Professor Dr. Peter Illes; Dr. Thomas Riedel
Subject Area
Clinical Neurology; Neurosurgery and Neuroradiology
Term
from 2007 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 22935240
P2X3 receptors are expressed with high selectivity in nociceptive dorsal root ganglion (DRG) neurons. Therefore, an intimate knowledge of the receptor-structure and -function is of utmost significance for the development of selective antagonists previously shown to be effective as therapeutic agents in various pain states. The experiments will be performed at HEK293 cells transfected with wild-type or mutant P2X3 or TRPV1 receptors, and in DRG neurons. We aim at investigating the following questions: A. Interaction between P2Y1 and P2X3 receptors. We intend to identify the second messenger pathways involved in this interaction. The most likely transduction mechanisms of the P2Y1 receptor include the Gq/11/phospholipase C/PKC and the Gq/11/phospholipase C/IP3/Ca2+ pathways or a membrane delimited inhibition via the ß¿ subunits.B. Interaction between P2X3 and TRPV1 receptors. We will investigate the negative interactionbetween these receptors co-localized at the same DRG neurons. C. Nucleotide binding sites and glycosylation sites. We have identified by molecular simulation the possible agonist binding sites and the glycosylation sites of the P2X3 receptor. Now we intend to experimentally confirm our predictions. D. Trafficking of P2X3 receptors. By means of confocal laser scanning microscopy we will follow the intracellular trafficking of these receptors.
DFG Programme
Research Units
