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Neuronal expression and regulation of CGRP promoter activity following viral gene transfer into cultured trigeminal ganglia neurons

Durham, PL ; Dong, PX ; Belasco, KT ; Kasperski, J ; Gierasch, WW ; Edvinsson, Lars LU ; Heistad, DD ; Faraci, FM and Russo, AF (2004) In Brain Research 997(1). p.103-110
Abstract
We have examined the regulation of calcitonin gene-related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in the heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was preferentially expressed in neurons, with 91% co-expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV-IacZ reporter was predominantly expressed in non-neuronal cells, with... (More)
We have examined the regulation of calcitonin gene-related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in the heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was preferentially expressed in neurons, with 91% co-expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV-IacZ reporter was predominantly expressed in non-neuronal cells, with only 29% co-expression with CGRP. We then asked whether the CGRP promoter in the viral vector could be regulated by serotonin receptor type 1 (5-HT1) agonists. Promoter activity was decreased two- to threefold by treatment with five 5-HTIB/D agonists, including the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for migraine treatment. As controls, CMV promoter activity was not affected, and 5-HTIB/D receptor antagonists blocked the repression caused by sumatriptan and eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis. (C) 2003 Elsevier B.V All rights reserved. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
trigeminal ganglia, gene expression, calcitonin gene-related peptide, adenovirus, migraine, 5-HT1 receptor
in
Brain Research
volume
997
issue
1
pages
103 - 110
publisher
Elsevier
external identifiers
  • pmid:14715155
  • wos:000188393700012
  • scopus:0347985815
ISSN
1872-6240
DOI
10.1016/j.brainres.2003.11.005
language
English
LU publication?
yes
id
626a5a83-73bb-4290-89f9-db5a5bc907b7 (old id 289507)
date added to LUP
2016-04-01 12:20:27
date last changed
2024-02-07 06:30:20
@article{626a5a83-73bb-4290-89f9-db5a5bc907b7,
  abstract     = {{We have examined the regulation of calcitonin gene-related peptide (CGRP) promoter activity in primary cultures of rat trigeminal ganglia neurons. A viral vector was used to circumvent the potential complication of examining only a small subpopulation of cells in the heterogeneous cultures. Infection with high titers of recombinant adenovirus containing 1.25 kb of the rat CGRP promoter linked to the beta-galactosidase reporter gene (AdCGRP-lacZ) yielded expression in about 50% of the CGRP-expressing neurons. The CGRP-lacZ reporter gene was preferentially expressed in neurons, with 91% co-expression with endogenous CGRP. In contrast, an adenoviral vector containing a CMV-IacZ reporter was predominantly expressed in non-neuronal cells, with only 29% co-expression with CGRP. We then asked whether the CGRP promoter in the viral vector could be regulated by serotonin receptor type 1 (5-HT1) agonists. Promoter activity was decreased two- to threefold by treatment with five 5-HTIB/D agonists, including the triptan drugs sumatriptan, eletriptan, and rizatriptan that are used for migraine treatment. As controls, CMV promoter activity was not affected, and 5-HTIB/D receptor antagonists blocked the repression caused by sumatriptan and eletriptan. Thus, adenoviral gene transfer can be used in trigeminal ganglia neurons for studying the mechanisms of triptan drug action on CGRP synthesis. (C) 2003 Elsevier B.V All rights reserved.}},
  author       = {{Durham, PL and Dong, PX and Belasco, KT and Kasperski, J and Gierasch, WW and Edvinsson, Lars and Heistad, DD and Faraci, FM and Russo, AF}},
  issn         = {{1872-6240}},
  keywords     = {{trigeminal ganglia; gene expression; calcitonin gene-related peptide; adenovirus; migraine; 5-HT1 receptor}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{103--110}},
  publisher    = {{Elsevier}},
  series       = {{Brain Research}},
  title        = {{Neuronal expression and regulation of CGRP promoter activity following viral gene transfer into cultured trigeminal ganglia neurons}},
  url          = {{http://dx.doi.org/10.1016/j.brainres.2003.11.005}},
  doi          = {{10.1016/j.brainres.2003.11.005}},
  volume       = {{997}},
  year         = {{2004}},
}