Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat

Edvinsson, Lars; Eftekhari, Sajedeh; Salvatore, Christopher; Warfvinge, Karin

doi:10.1016/j.mcn.2010.10.005

Cited by 76 publications

(70 citation statements)

References 24 publications

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“…the centre of motor coordination (Gustafson et al 2005;Ross et al 1990); more interestingly, in the human cerebellum, MrgE mRNA was found in Golgi cells, which are considered inhibitory interneurons, and in Purkinje cells, which perform inhibitory motor functions (Zhang et al 2005). Recent studies in the cerebellar biology indicate that there may be a role for this organ in nociception and mechanosensation (Duggan et al 2002;Edvinsson et al 2011). Taken together, all these data demonstrate that Mrg receptors are not exclusively expressed in sensory neurons, but also in some non-sensory neurons which may be involved in mechanosensation and nociception.…”

Section: Discussionmentioning

confidence: 99%

The effect of inflammation on the expression and distribution of the MAS-related gene receptors MrgE and MrgF in the murine ileum

Avula

Buckinx

Alpaerts

et al. 2011

Histochem Cell Biol

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The MAS-related gene (Mrg) receptor MrgE has been suggested to be expressed at all tissue levels involved in pain sensation and to influence the expression of another Mrg receptor, MrgF. Given the knowledge on the role of the enteric nervous system (ENS) in sensation, and the plasticity of enteric neurons during intestinal inflammation, it can be hypothesized that MrgE is expressed in enteric neurons, and that MrgE and MrgF change expression in intestinal inflammatory conditions. Therefore, we aimed to reveal the expression details of MrgE and MrgF in the murine ileum in normal and inflamed conditions. Using reverse transcriptase-PCR, quantitative-PCR and immunohistochemistry, we compared the ileum of non-inflamed control mice with that of two models of intestinal inflammation, i.e. intestinal schistosomiasis and chemically induced ileitis. MrgE and MrgF mRNAs were detected in control and inflamed conditions. MrgE and MrgF mRNAs showed a trend towards downregulation during intestinal schistosomiasis and a significant reduction during ileitis. MrgE and MrgF receptors were expressed in distinct enteric neuronal subpopulations, such as the sensory, secretomotor and vasodilator neurons, and in nerve fibres in the tunica muscularis and lamina propria of control and inflamed ileum. Only a minor proportion of enteric neurons co-expressed MrgE and MrgF. The number of enteric neurons expressing MrgE and MrgF receptors was significantly reduced during intestinal schistosomiasis and ileitis. This is the first report on the expression of MrgE and MrgF in the ENS in (patho)physiological conditions. The expression of MrgE and MrgF in enteric neurons was negatively affected by inflammation.

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Section: Discussionmentioning

confidence: 99%

The effect of inflammation on the expression and distribution of the MAS-related gene receptors MrgE and MrgF in the murine ileum

Avula

Buckinx

Alpaerts

et al. 2011

Histochem Cell Biol

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“…Direct autocrine regulation of the CGRP gene in trigeminal ganglia was demonstrated in primary cultures (39) and is supported by colocalization of CGRP and its receptor in presynaptic central terminals in situ (24, 90, 104). Investigators have also speculated that autocrine regulation of CGRP transcription occurs in the cerebellar Purkinje neurons (105). These positive feedback loops may explain why transgenic mice overexpressing the RAMP1 receptor subunit had elevated CGRP levels in cerebrospinal fluid (57).…”

Section: How Does Cgrp Contribute To Migraine?mentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

316

299

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Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.

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“…Many of these areas have been implicated in migraine (Raddant and Russo, 2011). CGRP-immunopositive cell bodies and fibers are found in hypothalamic nuclei, ventral tegmental area, cerebellum, and various brainstem nuclei, including the periaqueductal grey (PAG) (Dobolyi et al, 2005; Edvinsson et al, 2011; Kresse et al, 1995; Ma et al, 2003). Furthermore, CGRP-binding sites have been localized throughout the CNS including the cortex, limbic areas (e.g.…”

Section: Calcitonin Gene-related Peptide (Cgrp)mentioning

confidence: 99%

CGRP and migraine: Could PACAP play a role too?

Kaiser

Russo

2013

Neuropeptides

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Migraine is a debilitating neurological disorder that affects about 12% of the population. In the past decade, the role of the neuropeptide calcitonin gene-related peptide (CGRP) in migraine has been firmly established by clinical studies. CGRP administration can trigger migraines, and CGRP receptor antagonists ameliorate migraine. In this review, we will describe multifunctional activities of CGRP that could potentially contribute to migraine. These include roles in light aversion, neurogenic inflammation, peripheral and central sensitization of nociceptive pathways, cortical spreading depression, and regulation of nitric oxide production. Yet clearly there will be many other contributing genes that could act in concert with CGRP. One candidate is pituitary adenylate cyclase-activating peptide (PACAP), which shares some of the same actions as CGRP, including the ability to induce migraine in migraineurs and light aversive behavior in rodents. Interestingly, both CGRP and PACAP act on receptors that share an accessory subunit called receptor activity modifying protein-1 (RAMP1). Thus, comparisons between the actions of these two migraine-inducing neuropeptides, CGRP and PACAP, may provide new insights into migraine pathophysiology.

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Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat

Abstract: "Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat."

Cited by 76 publications

References 24 publications

The effect of inflammation on the expression and distribution of the MAS-related gene receptors MrgE and MrgF in the murine ileum

The effect of inflammation on the expression and distribution of the MAS-related gene receptors MrgE and MrgF in the murine ileum

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

CGRP and migraine: Could PACAP play a role too?

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