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Proteinase-activated receptor-1 activation presynaptically enhances spontaneous glutamatergic excitatory transmission in adult rat substantia gelatinosa neurons.
J Neurophysiol. 2009 Jul; 102(1):312-9.JN

Abstract

Proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. A potential impact of PAR on sensory processing has not been fully examined yet. Here we report that synthetic peptides with sequences corresponding to PAR ligands enhance glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. The frequency of spontaneous excitatory postsynaptic current (EPSC) was increased by PAR-1 agonist SFLLRN-NH2 (by 47% at 1 microM) with small increases by PAR-2 and -4 agonists (SLIGKV-NH2 and GYPGQV-OH, respectively; at >3 microM); there was no change in its amplitude or in holding current at -70 mV. The PAR-1 peptide action was inhibited by PAR-1 antagonist YFLLRNP-OH. TFLLR-NH2, an agonist which is more selective to PAR-1 than SFLLRN-NH2, dose-dependently increased spontaneous EPSC frequency (EC50=0.32 microM). A similar presynaptic effect was produced by PAR-1 activating proteinase thrombin in a manner sensitive to YFLLRNP-OH. The PAR-1 peptide action was resistant to tetrodotoxin and inhibited in Ca2+-free solution. Primary-afferent monosynaptically evoked EPSC amplitudes were unaffected by PAR-1 agonist. These results indicate that PAR-1 activation increases the spontaneous release of L-glutamate onto SG neurons from nerve terminals in a manner dependent on extracellular Ca2+. Considering that sensory processing within the SG plays a pivotal role in regulating nociceptive transmission to the spinal dorsal horn, the PAR-1-mediated glutamatergic transmission enhancement could be involved in a positive modulation of nociceptive transmission.

Authors+Show Affiliations

Department of Physiology, Saga Medical School, Saga 849-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19420120

Citation

Fujita, T, et al. "Proteinase-activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons." Journal of Neurophysiology, vol. 102, no. 1, 2009, pp. 312-9.
Fujita T, Liu T, Nakatsuka T, et al. Proteinase-activated receptor-1 activation presynaptically enhances spontaneous glutamatergic excitatory transmission in adult rat substantia gelatinosa neurons. J Neurophysiol. 2009;102(1):312-9.
Fujita, T., Liu, T., Nakatsuka, T., & Kumamoto, E. (2009). Proteinase-activated receptor-1 activation presynaptically enhances spontaneous glutamatergic excitatory transmission in adult rat substantia gelatinosa neurons. Journal of Neurophysiology, 102(1), 312-9. https://doi.org/10.1152/jn.91117.2008
Fujita T, et al. Proteinase-activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons. J Neurophysiol. 2009;102(1):312-9. PubMed PMID: 19420120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteinase-activated receptor-1 activation presynaptically enhances spontaneous glutamatergic excitatory transmission in adult rat substantia gelatinosa neurons. AU - Fujita,T, AU - Liu,T, AU - Nakatsuka,T, AU - Kumamoto,E, Y1 - 2009/05/06/ PY - 2009/5/8/entrez PY - 2009/5/8/pubmed PY - 2009/9/11/medline SP - 312 EP - 9 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 102 IS - 1 N2 - Proteinase-activated receptors (PARs) have a unique activation mechanism in that a proteolytically exposed N-terminal region acts as a tethered ligand. A potential impact of PAR on sensory processing has not been fully examined yet. Here we report that synthetic peptides with sequences corresponding to PAR ligands enhance glutamatergic excitatory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. The frequency of spontaneous excitatory postsynaptic current (EPSC) was increased by PAR-1 agonist SFLLRN-NH2 (by 47% at 1 microM) with small increases by PAR-2 and -4 agonists (SLIGKV-NH2 and GYPGQV-OH, respectively; at >3 microM); there was no change in its amplitude or in holding current at -70 mV. The PAR-1 peptide action was inhibited by PAR-1 antagonist YFLLRNP-OH. TFLLR-NH2, an agonist which is more selective to PAR-1 than SFLLRN-NH2, dose-dependently increased spontaneous EPSC frequency (EC50=0.32 microM). A similar presynaptic effect was produced by PAR-1 activating proteinase thrombin in a manner sensitive to YFLLRNP-OH. The PAR-1 peptide action was resistant to tetrodotoxin and inhibited in Ca2+-free solution. Primary-afferent monosynaptically evoked EPSC amplitudes were unaffected by PAR-1 agonist. These results indicate that PAR-1 activation increases the spontaneous release of L-glutamate onto SG neurons from nerve terminals in a manner dependent on extracellular Ca2+. Considering that sensory processing within the SG plays a pivotal role in regulating nociceptive transmission to the spinal dorsal horn, the PAR-1-mediated glutamatergic transmission enhancement could be involved in a positive modulation of nociceptive transmission. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/19420120/Proteinase_activated_receptor_1_activation_presynaptically_enhances_spontaneous_glutamatergic_excitatory_transmission_in_adult_rat_substantia_gelatinosa_neurons_ L2 - http://www.physiology.org/doi/full/10.1152/jn.91117.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -