PMID- 17064360
OWN - NLM
STAT- MEDLINE
DCOM- 20070123
LR  - 20220318
IS  - 0022-3042 (Print)
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 99
IP  - 5
DP  - 2006 Dec
TI  - Calcitonin gene-related peptide enhances release of native brain-derived 
      neurotrophic factor from trigeminal ganglion neurons.
PG  - 1338-50
AB  - Activity-dependent plasticity in nociceptive pathways has been implicated in 
      pathomechanisms of chronic pain syndromes. Calcitonin gene-related peptide 
      (CGRP), which is expressed by trigeminal nociceptors, has recently been 
      identified as a key player in the mechanism of migraine headaches. Here we show 
      that CGRP is coexpressed with brain-derived neurotrophic factor (BDNF) in a large 
      subset of adult rat trigeminal ganglion neurons in vivo. Using ELISA in situ, we 
      show that CGRP (1-1000 nM) potently enhances BDNF release from cultured 
      trigeminal neurons. The effect of CGRP is dose-dependent and abolished by 
      pretreatment with CGRP receptor antagonist, CGRP(8-37). Intriguingly, 
      CGRP-mediated BDNF release, unlike BDNF release evoked by physiological patterns 
      of electrical stimulation, is independent of extracellular calcium. Depletion of 
      intracellular calcium stores with thapsigargin blocks the CGRP-mediated BDNF 
      release. Using transmission electron microscopy, our study also shows that 
      BDNF-immunoreactivity is present in dense core vesicles of unmyelinated axons and 
      axon terminals in the subnucleus caudalis of the spinal trigeminal nucleus, the 
      primary central target of trigeminal nociceptors. Together, these results reveal 
      a previously unknown role for CGRP in regulating BDNF availability, and point to 
      BDNF as a candidate mediator of trigeminal nociceptive plasticity.
FAU - Buldyrev, Ilya
AU  - Buldyrev I
AD  - Department of Integrative Biosciences, Oregon Health and Science University, 
      Portland, Oregon 97239, USA.
FAU - Tanner, Nathan M
AU  - Tanner NM
FAU - Hsieh, Hui-ya
AU  - Hsieh HY
FAU - Dodd, Emily G
AU  - Dodd EG
FAU - Nguyen, Loi T
AU  - Nguyen LT
FAU - Balkowiec, Agnieszka
AU  - Balkowiec A
LA  - eng
GR  - R01 HL076113-01A1/HL/NHLBI NIH HHS/United States
GR  - HL076113/HL/NHLBI NIH HHS/United States
GR  - 5T32NS007466/NS/NINDS NIH HHS/United States
GR  - R01 HL076113-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL076113/HL/NHLBI NIH HHS/United States
GR  - T32 NS007466/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061025
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcitonin Gene-Related Peptide Receptor Antagonists)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Calcitonin Gene-Related Peptide)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcitonin Gene-Related Peptide/pharmacology/*physiology
MH  - Calcitonin Gene-Related Peptide Receptor Antagonists
MH  - Calcium Signaling/drug effects/physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Electric Stimulation
MH  - Male
MH  - Microscopy, Immunoelectron
MH  - Migraine Disorders/metabolism/physiopathology
MH  - Neuronal Plasticity/physiology
MH  - Neurons, Afferent/drug effects/*metabolism/ultrastructure
MH  - Nociceptors/*metabolism
MH  - Pain/chemically induced/*metabolism/physiopathology
MH  - Peptide Fragments/pharmacology
MH  - Presynaptic Terminals/metabolism/ultrastructure
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Calcitonin Gene-Related Peptide/metabolism
MH  - Trigeminal Caudal Nucleus/metabolism/ultrastructure
MH  - Trigeminal Ganglion/*metabolism/physiopathology/ultrastructure
PMC - PMC2440676
MID - NIHMS54951
EDAT- 2006/10/27 09:00
MHDA- 2007/01/24 09:00
PMCR- 2008/06/26
CRDT- 2006/10/27 09:00
PHST- 2006/10/27 09:00 [pubmed]
PHST- 2007/01/24 09:00 [medline]
PHST- 2006/10/27 09:00 [entrez]
PHST- 2008/06/26 00:00 [pmc-release]
AID - JNC4161 [pii]
AID - 10.1111/j.1471-4159.2006.04161.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Dec;99(5):1338-50. doi: 10.1111/j.1471-4159.2006.04161.x. Epub 
      2006 Oct 25.