Release of glutamate and CGRP from trigeminal ganglion neurons: Role of calcium channels and 5-HT1 receptor signaling

Yan Xiao, Judith A. Richter, Joyce Hurley

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Background: The aberrant release of the neurotransmitters, glutamate and calcitonin-gene related peptide (CGRP), from trigeminal neurons has been implicated in migraine. The voltage-gated P/Q-type calcium channel has a critical role in controlling neurotransmitter release and has been linked to Familial Hemiplegic Migraine. Therefore, we examined the importance of voltage-dependent calcium channels in controlling release of glutamate and CGRP from trigeminal ganglion neurons isolated from male and female rats and grown in culture. Serotonergic pathways are likely involved in migraine, as triptans, a class of 5-HT1 receptor agonists, are effective in the treatment of migraine and their effectiveness may be due to inhibiting neurotransmitter release from trigeminal neurons. We also studied the effect of serotonin receptor activation on release of glutamate and CGRP from trigeminal neurons grown in culture. Results: P/Q-, N- and L-type channels each mediate a significant fraction of potassium-stimulated release of glutamate and CGRP. We determined that 5-HT significantly inhibits potassium-stimulated release of both glutamate and CGRP. Serotonergic inhibition of both CGRP and glutamate release can be blocked by pertussis toxin and NAS-181, a 5-HT1B/1D antagonist. Stimulated release of CGRP is unaffected by Y-25130, a 5-HT3 antagonist and SB 200646, a 5-HT2B/2C antagonist. Conclusion: These data suggest that release of both glutamate and CGRP from trigeminal neurons is controlled by calcium channels and modulated by 5-HT signaling in a pertussis-toxin dependent manner and probably via 5-HT1 receptor signaling. This is the first characterization of glutamate release from trigeminal neurons grown in culture.

Original languageEnglish
Article number12
JournalMolecular Pain
Volume4
DOIs
StatePublished - Apr 16 2008

Fingerprint

Serotonin 5-HT1 Receptors
Trigeminal Ganglion
Calcitonin Gene-Related Peptide
Calcium Channels
Glutamic Acid
Neurons
Migraine Disorders
Neurotransmitter Agents
Pertussis Toxin
Serotonin
Potassium
Q-Type Calcium Channels
P-Type Calcium Channels
Serotonin 5-HT1 Receptor Antagonists
Tryptamines
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT3 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Migraine with Aura
Serotonin Receptors

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Release of glutamate and CGRP from trigeminal ganglion neurons : Role of calcium channels and 5-HT1 receptor signaling. / Xiao, Yan; Richter, Judith A.; Hurley, Joyce.

In: Molecular Pain, Vol. 4, 12, 16.04.2008.

Research output: Contribution to journalArticle

@article{836fbadf92d442beb955644d3f735e7c,
title = "Release of glutamate and CGRP from trigeminal ganglion neurons: Role of calcium channels and 5-HT1 receptor signaling",
abstract = "Background: The aberrant release of the neurotransmitters, glutamate and calcitonin-gene related peptide (CGRP), from trigeminal neurons has been implicated in migraine. The voltage-gated P/Q-type calcium channel has a critical role in controlling neurotransmitter release and has been linked to Familial Hemiplegic Migraine. Therefore, we examined the importance of voltage-dependent calcium channels in controlling release of glutamate and CGRP from trigeminal ganglion neurons isolated from male and female rats and grown in culture. Serotonergic pathways are likely involved in migraine, as triptans, a class of 5-HT1 receptor agonists, are effective in the treatment of migraine and their effectiveness may be due to inhibiting neurotransmitter release from trigeminal neurons. We also studied the effect of serotonin receptor activation on release of glutamate and CGRP from trigeminal neurons grown in culture. Results: P/Q-, N- and L-type channels each mediate a significant fraction of potassium-stimulated release of glutamate and CGRP. We determined that 5-HT significantly inhibits potassium-stimulated release of both glutamate and CGRP. Serotonergic inhibition of both CGRP and glutamate release can be blocked by pertussis toxin and NAS-181, a 5-HT1B/1D antagonist. Stimulated release of CGRP is unaffected by Y-25130, a 5-HT3 antagonist and SB 200646, a 5-HT2B/2C antagonist. Conclusion: These data suggest that release of both glutamate and CGRP from trigeminal neurons is controlled by calcium channels and modulated by 5-HT signaling in a pertussis-toxin dependent manner and probably via 5-HT1 receptor signaling. This is the first characterization of glutamate release from trigeminal neurons grown in culture.",
author = "Yan Xiao and Richter, {Judith A.} and Joyce Hurley",
year = "2008",
month = "4",
day = "16",
doi = "10.1186/1744-8069-4-12",
language = "English",
volume = "4",
journal = "Molecular Pain",
issn = "1744-8069",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Release of glutamate and CGRP from trigeminal ganglion neurons

T2 - Role of calcium channels and 5-HT1 receptor signaling

AU - Xiao, Yan

AU - Richter, Judith A.

AU - Hurley, Joyce

PY - 2008/4/16

Y1 - 2008/4/16

N2 - Background: The aberrant release of the neurotransmitters, glutamate and calcitonin-gene related peptide (CGRP), from trigeminal neurons has been implicated in migraine. The voltage-gated P/Q-type calcium channel has a critical role in controlling neurotransmitter release and has been linked to Familial Hemiplegic Migraine. Therefore, we examined the importance of voltage-dependent calcium channels in controlling release of glutamate and CGRP from trigeminal ganglion neurons isolated from male and female rats and grown in culture. Serotonergic pathways are likely involved in migraine, as triptans, a class of 5-HT1 receptor agonists, are effective in the treatment of migraine and their effectiveness may be due to inhibiting neurotransmitter release from trigeminal neurons. We also studied the effect of serotonin receptor activation on release of glutamate and CGRP from trigeminal neurons grown in culture. Results: P/Q-, N- and L-type channels each mediate a significant fraction of potassium-stimulated release of glutamate and CGRP. We determined that 5-HT significantly inhibits potassium-stimulated release of both glutamate and CGRP. Serotonergic inhibition of both CGRP and glutamate release can be blocked by pertussis toxin and NAS-181, a 5-HT1B/1D antagonist. Stimulated release of CGRP is unaffected by Y-25130, a 5-HT3 antagonist and SB 200646, a 5-HT2B/2C antagonist. Conclusion: These data suggest that release of both glutamate and CGRP from trigeminal neurons is controlled by calcium channels and modulated by 5-HT signaling in a pertussis-toxin dependent manner and probably via 5-HT1 receptor signaling. This is the first characterization of glutamate release from trigeminal neurons grown in culture.

AB - Background: The aberrant release of the neurotransmitters, glutamate and calcitonin-gene related peptide (CGRP), from trigeminal neurons has been implicated in migraine. The voltage-gated P/Q-type calcium channel has a critical role in controlling neurotransmitter release and has been linked to Familial Hemiplegic Migraine. Therefore, we examined the importance of voltage-dependent calcium channels in controlling release of glutamate and CGRP from trigeminal ganglion neurons isolated from male and female rats and grown in culture. Serotonergic pathways are likely involved in migraine, as triptans, a class of 5-HT1 receptor agonists, are effective in the treatment of migraine and their effectiveness may be due to inhibiting neurotransmitter release from trigeminal neurons. We also studied the effect of serotonin receptor activation on release of glutamate and CGRP from trigeminal neurons grown in culture. Results: P/Q-, N- and L-type channels each mediate a significant fraction of potassium-stimulated release of glutamate and CGRP. We determined that 5-HT significantly inhibits potassium-stimulated release of both glutamate and CGRP. Serotonergic inhibition of both CGRP and glutamate release can be blocked by pertussis toxin and NAS-181, a 5-HT1B/1D antagonist. Stimulated release of CGRP is unaffected by Y-25130, a 5-HT3 antagonist and SB 200646, a 5-HT2B/2C antagonist. Conclusion: These data suggest that release of both glutamate and CGRP from trigeminal neurons is controlled by calcium channels and modulated by 5-HT signaling in a pertussis-toxin dependent manner and probably via 5-HT1 receptor signaling. This is the first characterization of glutamate release from trigeminal neurons grown in culture.

UR - http://www.scopus.com/inward/record.url?scp=43049119638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43049119638&partnerID=8YFLogxK

U2 - 10.1186/1744-8069-4-12

DO - 10.1186/1744-8069-4-12

M3 - Article

C2 - 18416824

AN - SCOPUS:43049119638

VL - 4

JO - Molecular Pain

JF - Molecular Pain

SN - 1744-8069

M1 - 12

ER -