Abstract | BACKGROUND AND OBJECTIVE: EXPERIMENTAL PROCEDURES: Sections of adult rat trigeminal ganglia were cultured for up to 48 hours, examined with immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) assay. Specific antibodies against CGRP, phosphorylated ERK1/2 (pERK1/2), total ERK1/2 (tERK1/2), phosphorylated p38 (pp38), phosphorylated C-Jun-N-terminal protein kinase (pJNK), pro-calcitonin (pro-CT), CGRP receptor activity modifying protein 1 (RAMP1), glutamine synthetase (GS) and pro-CT were used. To explore molecular mechanisms involved in the organ culture-induced CGRP-ir in neurons and glial cells, the effects of the MEK/ERK1/2 inhibitor U0126, its inactive analogue U0124, the p38 inhibitor SB203580 and the JNK inhibitor SP600125 were studied. RESULTS: In fresh ganglia, small- and medium-sized neurons were CGRP-ir while some larger neurons displayed RAMP1-ir. Glial cells were negative to both. After organ culture, neurons showed enhanced CGRP- and RAMP1-ir. In addition, some glial cells were RAMP1- and CGRP-ir. Isolated glial cells and neurons were found to contain CGRP mRNA, and showed pro-CT-ir, suggestive of local formation of CGRP. Neurons and glial cells showed enhanced pERK1/2-ir already after two hours of organ culture and this remained elevated for 48 hours. There was transient pJNK-ir in neurons at two hours, while pp38-ir was not altered. U0126 reduced the enhanced pERK1/2-ir, while U0124 had no such effect; the CGRP-ir in neurons and glial cells was reduced at 48 hours and in parallel the CGRP mRNA expression was lower at 24 hours. CONCLUSION: We suggest that in conditions of elevated CGRP expression, inhibition of ERK1/2 might be an option for novel treatment.
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Authors | János Tajti, Anikó Kuris, László Vécsei, Cang-Bao Xu, Lars Edvinsson |
Journal | Cephalalgia : an international journal of headache
(Cephalalgia)
Vol. 31
Issue 1
Pg. 95-105
(Jan 2011)
ISSN: 1468-2982 [Electronic] England |
PMID | 20851839
(Publication Type: Journal Article)
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Chemical References |
- Enzyme Inhibitors
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Calcitonin Gene-Related Peptide
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Topics |
- Animals
- Calcitonin Gene-Related Peptide
(biosynthesis)
- Enzyme Activation
(physiology)
- Enzyme Inhibitors
(pharmacology)
- Image Processing, Computer-Assisted
- Immunohistochemistry
- Male
- Mitogen-Activated Protein Kinase 1
(biosynthesis)
- Mitogen-Activated Protein Kinase 3
(biosynthesis)
- Neuroglia
(metabolism)
- Neurons
(metabolism)
- Organ Culture Techniques
- Rats
- Rats, Sprague-Dawley
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(drug effects, physiology)
- Trigeminal Ganglion
(cytology, metabolism)
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