Abstract
Proteinase-activated receptors (PARs), PAR-1 to -4, are activated by selective proteinases which expose their new N-terminal regions as tethered ligands. PAR-1, -2, and -4 can be also activated by synthetic peptides corresponding to the individual tethered ligands without proteinases. Although PARs are reported to be involved in nociceptive transmission in peripheral terminals of primary afferents, it has not been clarified yet whether PARs are activated in the spinal dorsal horn. We previously found that PAR-1 agonist peptides, SFLLRN and TFLLR, reversibly increase the frequency of glutamatergic spontaneous excitatory postsynaptic current without a change in the amplitude in substantia gelatinosa (SG) neurons, which are thought to play a pivotal role in regulating nociceptive transmission. In the present study, we further examined the enhancement of excitatory transmission by PAR-1 agonists by applying the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. The presynaptic effect of SFLLRN was not seen in a nominally Ca2+-free solution. Similar facilitatory effects were produced by endogenous PAR-1 activating proteinases, thrombin and trypsin. All of the PAR-1 agonists tested did not alter holding currents at -70 mV. These results indicate that not only exogenous but also endogenous PAR-1 agonists enhance the spontaneous release of L-glutamate from nerve terminals in the SG, probably through Ca2+ entry from extracellular solution; this presynaptic action may play a role in producing nociception. [J Physiol Sci. 2008;58 Suppl:S133]
