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5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons.
Br J Pharmacol. 2012 Sep; 167(2):356-67.BJ

Abstract

BACKGROUND AND PURPOSE

Although 5-HT(1B) receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons.

EXPERIMENTAL APPROACH

Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition.

KEY RESULTS

CP93129, a selective 5-HT(1B) receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D) receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist. Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker.

CONCLUSIONS AND IMPLICATIONS

The present results suggest that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT(1B) receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues.

Authors+Show Affiliations

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

22462474

Citation

Choi, I-S, et al. "5-HT(1B) Receptors Inhibit Glutamate Release From Primary Afferent Terminals in Rat Medullary Dorsal Horn Neurons." British Journal of Pharmacology, vol. 167, no. 2, 2012, pp. 356-67.
Choi IS, Cho JH, An CH, et al. 5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons. Br J Pharmacol. 2012;167(2):356-67.
Choi, I. S., Cho, J. H., An, C. H., Jung, J. K., Hur, Y. K., Choi, J. K., & Jang, I. S. (2012). 5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons. British Journal of Pharmacology, 167(2), 356-67. https://doi.org/10.1111/j.1476-5381.2012.01964.x
Choi IS, et al. 5-HT(1B) Receptors Inhibit Glutamate Release From Primary Afferent Terminals in Rat Medullary Dorsal Horn Neurons. Br J Pharmacol. 2012;167(2):356-67. PubMed PMID: 22462474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons. AU - Choi,I-S, AU - Cho,J-H, AU - An,C-H, AU - Jung,J-K, AU - Hur,Y-K, AU - Choi,J-K, AU - Jang,I-S, PY - 2012/4/3/entrez PY - 2012/4/3/pubmed PY - 2013/1/8/medline SP - 356 EP - 67 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 167 IS - 2 N2 - BACKGROUND AND PURPOSE: Although 5-HT(1B) receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons. EXPERIMENTAL APPROACH: Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition. KEY RESULTS: CP93129, a selective 5-HT(1B) receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D) receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist. Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker. CONCLUSIONS AND IMPLICATIONS: The present results suggest that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT(1B) receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/22462474/5_HT_1B__receptors_inhibit_glutamate_release_from_primary_afferent_terminals_in_rat_medullary_dorsal_horn_neurons_ L2 - https://doi.org/10.1111/j.1476-5381.2012.01964.x DB - PRIME DP - Unbound Medicine ER -