title: 5-HT(1B)  receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.affiliation: Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: I-S
authors.initials: IS
authors.lastname: Choi
authors.forename: J-H
authors.initials: JH
authors.lastname: Cho
authors.forename: C-H
authors.initials: CH
authors.lastname: An
authors.forename: J-K
authors.initials: JK
authors.lastname: Jung
authors.forename: Y-K
authors.initials: YK
authors.lastname: Hur
authors.forename: J-K
authors.initials: JK
authors.lastname: Choi
authors.forename: I-S
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D055724:Electrophysiological Phenomena; D018698:Glutamic Acid / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*
chemical_list: D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D018698:Glutamic Acid