Tags

Type your tag names separated by a space and hit enter

Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice.
Neurosci Lett 2016; 620:104-10NL

Abstract

Migraine is a neurovascular brain disorder suggested to be due to dysfunction of the trigeminovascular system with sensitization of trigeminal ganglion (TG) nociceptors. Since the neuropeptide calcitonin gene-related peptide (CGRP) has been established as a key player in the pathogenesis of migraine, CGRP receptor antagonists have been considered useful compounds to block headache originating from hyperactivation of such TG neurons. Whereas there is some information on the expression of CGRP receptors in postmortem human tissue, data are lacking for migraineurs suffering from common or genetic migraine. To help to clarify these issues it is very useful to study a transgenic knock-in (KI) mouse model of hemiplegic migraine expressing a R192Q missense mutation in the α1 subunit of CaV2.1 calcium channels previously found in patients with familial hemiplegic migraine type-1 (FHM-1). The aim of the present study, therefore, was to compare CGRP receptor expression and function in wildtype (WT) versus KI mouse TG. The principal components of the CGRP receptor, namely the CLR and RAMP-1 proteins, were similarly expressed in WT and KI TG neurons (in situ or in culture) and responded to exogenous CGRP with a strong rise in cAMP concentration. Hence, the previously reported phenotype of sensitization of KI TG neurons is not due to up-regulation of CGRP receptors but is likely caused by a constitutively larger release of CGRP. This observation implies that, in FHM-1 TG, normal TG sensory neuron signaling can be restored once the extracellular concentration of CGRP returns to control level with targeted treatment.

Authors+Show Affiliations

Neuroscience Department, International School for Advanced Studies (SISSA), Trieste, Italy. Electronic address: vilotti@sissa.it.Neuroscience Department, International School for Advanced Studies (SISSA), Trieste, Italy. Electronic address: nv1e15@soton.ac.uk.Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands; Department of Human Genetics, University Medical Centre, Leiden, Netherlands. Electronic address: A.M.J.M.van_den_Maagdenberg@lumc.nl.Neuroscience Department, International School for Advanced Studies (SISSA), Trieste, Italy. Electronic address: nistri@sissa.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27021026

Citation

Vilotti, Sandra, et al. "Expression and Function of Calcitonin Gene-related Peptide (CGRP) Receptors in Trigeminal Ganglia of R192Q Cacna1a Knock-in Mice." Neuroscience Letters, vol. 620, 2016, pp. 104-10.
Vilotti S, Vana N, Van den Maagdenberg AM, et al. Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice. Neurosci Lett. 2016;620:104-10.
Vilotti, S., Vana, N., Van den Maagdenberg, A. M., & Nistri, A. (2016). Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice. Neuroscience Letters, 620, pp. 104-10. doi:10.1016/j.neulet.2016.03.046.
Vilotti S, et al. Expression and Function of Calcitonin Gene-related Peptide (CGRP) Receptors in Trigeminal Ganglia of R192Q Cacna1a Knock-in Mice. Neurosci Lett. 2016 05 4;620:104-10. PubMed PMID: 27021026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and function of calcitonin gene-related peptide (CGRP) receptors in trigeminal ganglia of R192Q Cacna1a knock-in mice. AU - Vilotti,Sandra, AU - Vana,Natascha, AU - Van den Maagdenberg,Arn M J M, AU - Nistri,Andrea, Y1 - 2016/03/25/ PY - 2016/02/22/received PY - 2016/03/22/revised PY - 2016/03/24/accepted PY - 2016/3/30/entrez PY - 2016/3/30/pubmed PY - 2017/7/25/medline KW - CGRP receptor KW - CLR KW - Familial hemiplegic migraine type-1 KW - Nociception KW - RAMP1 KW - cAMP SP - 104 EP - 10 JF - Neuroscience letters JO - Neurosci. Lett. VL - 620 N2 - Migraine is a neurovascular brain disorder suggested to be due to dysfunction of the trigeminovascular system with sensitization of trigeminal ganglion (TG) nociceptors. Since the neuropeptide calcitonin gene-related peptide (CGRP) has been established as a key player in the pathogenesis of migraine, CGRP receptor antagonists have been considered useful compounds to block headache originating from hyperactivation of such TG neurons. Whereas there is some information on the expression of CGRP receptors in postmortem human tissue, data are lacking for migraineurs suffering from common or genetic migraine. To help to clarify these issues it is very useful to study a transgenic knock-in (KI) mouse model of hemiplegic migraine expressing a R192Q missense mutation in the α1 subunit of CaV2.1 calcium channels previously found in patients with familial hemiplegic migraine type-1 (FHM-1). The aim of the present study, therefore, was to compare CGRP receptor expression and function in wildtype (WT) versus KI mouse TG. The principal components of the CGRP receptor, namely the CLR and RAMP-1 proteins, were similarly expressed in WT and KI TG neurons (in situ or in culture) and responded to exogenous CGRP with a strong rise in cAMP concentration. Hence, the previously reported phenotype of sensitization of KI TG neurons is not due to up-regulation of CGRP receptors but is likely caused by a constitutively larger release of CGRP. This observation implies that, in FHM-1 TG, normal TG sensory neuron signaling can be restored once the extracellular concentration of CGRP returns to control level with targeted treatment. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/27021026/Expression_and_function_of_calcitonin_gene_related_peptide__CGRP__receptors_in_trigeminal_ganglia_of_R192Q_Cacna1a_knock_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(16)30184-7 DB - PRIME DP - Unbound Medicine ER -