Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence and autoradiography.
(2016) In Journal of Comparative Neurology 524(1). p.90-118- Abstract
- Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was... (More)
- Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7478075
- author
- Eftekhari, Sajedeh LU ; Gaspar, Renee C ; Roberts, Rhonda ; Chen, Tsing-Bau ; Zeng, Zhizhen ; Villarreal, Stephanie ; Edvinsson, Lars and Salvatore, Christopher A
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Comparative Neurology
- volume
- 524
- issue
- 1
- pages
- 90 - 118
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:26105175
- wos:000365719500007
- scopus:84948104998
- pmid:26105175
- ISSN
- 1096-9861
- DOI
- 10.1002/cne.23828
- language
- English
- LU publication?
- yes
- id
- 05aa1b26-118d-4c79-906f-0c2b4e50d7f0 (old id 7478075)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26105175?dopt=Abstract
- date added to LUP
- 2016-04-01 10:27:23
- date last changed
- 2024-02-21 16:51:53
@article{05aa1b26-118d-4c79-906f-0c2b4e50d7f0,
abstract = {{Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus and spinal trigeminal nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, motor trigeminal nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved.}},
author = {{Eftekhari, Sajedeh and Gaspar, Renee C and Roberts, Rhonda and Chen, Tsing-Bau and Zeng, Zhizhen and Villarreal, Stephanie and Edvinsson, Lars and Salvatore, Christopher A}},
issn = {{1096-9861}},
language = {{eng}},
number = {{1}},
pages = {{90--118}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Comparative Neurology}},
title = {{Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence and autoradiography.}},
url = {{http://dx.doi.org/10.1002/cne.23828}},
doi = {{10.1002/cne.23828}},
volume = {{524}},
year = {{2016}},
}