CGRP: a Multifunctional Neuropeptide

Russo, Andrew F.; Dickerson, Ian M.

doi:10.1007/0-387-30395-2_19

Cited by 6 publications

(17 citation statements)

References 319 publications

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“…159 Consequently, there is overlap among activities of CGRP, AMY, and AM in this family of receptors. 159,160,190 The proposed CGRP 2 receptor has never been identified, and it is believed that this was an artifact because of the ability of CGRP to bind to the AM and AMY receptors. Expression cloning strategies, which successfully cloned the CT receptor, were applied to the search for the CGRP receptor.…”

Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

“…For example, CGRP binds to the AMY1 receptor (ie, CT/RAMP1), although at one-tenth the affinity of AMY itself, and this affinity may account for the reported displacement of AMY by CGRP in the nucleus accumbens. 42,160 Thus, although CGRP acts most prominently via the CGRP receptor, it is nonetheless capable of exerting functional activity through these related receptors as well. Notably, however, a recent study using TaqMan G protein–coupled receptor arrays and immunohistochemistry found that the AMY1 receptor has high affinity for CGRP that is comparable with the CGRP receptor, and proposed that it be considered as a dual CGRP/AMY receptor.…”

Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

“…185 In addition to CLR and the RAMPs, a third protein, the receptor component protein, is important for the full expression of the CGRP receptor activity. 159,160,190 This protein is responsible for effective coupling of the CLR to the Gα s subunit, allowing activation of adenylate cyclase. 159 …”

Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

“…In contrast to many G-protein–coupled receptors, the CGRP receptor requires the heterodimerization of 2 components, the receptor activity–modifying protein 1 (RAMP1) accessory protein and the calcitonin receptor–like receptor (CLR) protein, to efficiently couple to the G s subunit. 152,159,160,190 Moreover, CGRP has affinity to other receptors, including the amylin 1 (AMY1) receptor, which is also a heterodimer containing RAMP1 but with the calcitonin receptor (CT) protein. 159,160,190 Calcitonin gene–related peptide's affinity for AMY1 is comparable with the CGRP receptor, and has been proposed as a second CGRP receptor site.…”

Section: Introductionmentioning

confidence: 99%

“…152,159,160,190 Moreover, CGRP has affinity to other receptors, including the amylin 1 (AMY1) receptor, which is also a heterodimer containing RAMP1 but with the calcitonin receptor (CT) protein. 159,160,190 Calcitonin gene–related peptide's affinity for AMY1 is comparable with the CGRP receptor, and has been proposed as a second CGRP receptor site. 185 In addition to its role in the somatosensory system, CGRP is also an extremely potent vasodilator, and vascular beds, including the mesenteric and the meningeal vasculatures, richly express CGRP receptors.…”

Section: Introductionmentioning

confidence: 99%

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The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

Iyengar

Ossipov²,

Johnson

2017

Pain

458

364

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Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

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Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

Section: Calcitonin Gene–related Peptide and The Calcitonin Gene–rmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

Iyengar

Ossipov²,

Johnson

2017

Pain

458

364

View full text Add to dashboard Cite

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Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

Raddant

Russo

2011

Expert Rev. Mol. Med.

173

153

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Over the past two decades, a convergence of basic and clinical evidence has established the neuropeptide calcitonin-gene-related peptide (CGRP) as a key player in migraine. Although CGRP is a recognised neuromodulator of nociception, its mechanism of action in migraine remains elusive. In this review, we present evidence that led us to propose that CGRP is well poised to enhance neurotransmission in migraine by both peripheral and central mechanisms. In the periphery, it is thought that local release of CGRP from the nerve endings of meningeal nociceptors following their initial activation by cortical spreading depression is critical for the induction of vasodilation, plasma protein extravasation, neurogenic inflammation and the consequential sensitisation of meningeal nociceptors. Mechanistically, we propose that CGRP release can give rise to a positive-feedback loop involved in localised increased synthesis and release of CGRP from neurons and a CGRP-like peptide called procalcitonin from trigeminal ganglion glia. Within the brain, the wide distribution of CGRP and CGRP receptors provides numerous possible targets for CGRP to act as a neuromodulator.

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CGRP and the Trigeminal System in Migraine

et al. 2019

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Objective The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system. Background Migraine is a prevalent and disabling neurological disease that is characterized in part by intense, throbbing, and unilateral headaches. Despite recent advances in understanding its pathophysiology, migraine still represents an unmet medical need, as it is often underrecognized and undertreated. Although CGRP has been known to play a pivotal role in migraine for the last 2 decades, this has now received more interest spurred by the early clinical successes of drugs that block CGRP signaling in the trigeminovascular system. Design This narrative review presents an update on the role of CGRP within the trigeminovascular system. PubMed searches were used to find recent (ie, 2016 to November 2018) published articles presenting new study results. Review articles are also included not as primary references but to bring these to the attention of the reader. Original research is referenced in describing the core of the narrative, and review articles are used to support ancillary points. Results The trigeminal ganglion neurons provide the connection between the periphery, stemming from the interface between the primary afferent fibers of the trigeminal ganglion and the meningeal vasculature and the central terminals in the trigeminal nucleus caudalis. The neuropeptide CGRP is abundant in trigeminal ganglion neurons, and is released from the peripheral nerve and central nerve terminals as well as being secreted within the trigeminal ganglion. Release of CGRP from the peripheral terminals initiates a cascade of events that include increased synthesis of nitric oxide and sensitization of the trigeminal nerves. Secreted CGRP in the trigeminal ganglion interacts with adjacent neurons and satellite glial cells to perpetuate peripheral sensitization, and can drive central sensitization of the second‐order neurons. A shift in central sensitization from activity‐dependent to activity‐independent central sensitization may indicate a mechanism driving the progression of episodic migraine to chronic migraine. The pathophysiology of cluster headache is much more obscure than that of migraine, but emerging evidence suggests that it may also involve hypersensitivity of the trigeminovascular system. Ongoing clinical studies with therapies targeted at CGRP will provide additional, valuable insights into the pathophysiology of this disorder. Conclusions CGRP plays an essential role in the pathophysiology of migraine. Treatments that interfere with the functioning of CGRP in the peripheral trigeminal system are effective against migraine. Blocking sensitization of the trigeminal nerve by attenuating CGRP activity in the periphery may be sufficient to block a migraine attack. Addit...

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CGRP: a Multifunctional Neuropeptide

Cited by 6 publications

References 319 publications

The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation

CGRP and the Trigeminal System in Migraine

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