Abstract
G-protein coupled proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. Four members of PARs such as PAR-1 and PAR-2, which were identified by molecular cloning, can be activated by synthetic peptides whose amino acid sequences correspond to the tethered ligands. Although PARs appear to be involved in nociceptive transmission in peripheral terminals of primary afferents, there is no report about involvement of PARs in the transmission in the spinal dorsal horn. In order to clarify a role of PARs in the nociceptive transmission, we examined how PAR-1 and PAR-2 agonist peptides affect glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) in substantia gelatinosa (SG; lamina II of Rexed) neurons which are thought to play a pivotal role in regulating nociceptive transmission to the CNS. We applied the blind whole-cell voltage-clamp technique to the SG neurons in adult rat spinal cord slices. PAR-1 agonist peptide (SFLLRN-NH2; 1 μM) reversibly increased the frequency of sEPSC without a change in its amplitude, while PAR-2 agonist peptide (SLIGKV-NH2; 1 μM) had no effects on sEPSCs. Both peptides did not alter holding currents at -70 mV. These results indicate that PAR-1 but not PAR-2 agonist peptide enhances the spontaneous release of L-glutamate from nerve terminals in the SG. It is suggested that PAR-1s expressed in nerve terminals in the SG may play an important role in producing nociception. [J Physiol Sci. 2006;56 Suppl:S162]
