Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro

Ebersberger, Andrea; Averbeck, Beate; Meßlinger, Karl; Reeh, Peter W.

doi:10.1016/s0306-4522(98)00366-2

Cited by 185 publications

(156 citation statements)

References 56 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…NO gas caused an elevation in CGRP release as well. In the same preparation, Ebersberger et al [32]showed that antidromic electrical stimulation of dural afferents as well as local application of inflammatory mediators or low pH released CGRP and PGE 2 from the dura mater. Release of CGRP upon afferent stimulation is implicated in physiological and pathophysiological reactions associated with increased perfusion of tissues [38], but there are only a few reports suggesting that NO can stimulate CGRP release.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

2002

View full text Add to dashboard Cite

Nitric oxide (NO) and calcitonin-gene-related peptide (CGRP) are implicated in the pathophysiology of vascular headaches. We studied the interaction of these two vasodilatory mediators in an animal model and suggest that NO may increase meningeal blood flow not only by its direct vasodilatory action but also by stimulating CGRP release. First, CGRP release from the rat cranial dura mater was measured in vitro using an enzyme immunoassay. Hemisected skulls with adhering dura mater were filled with synthetic interstitial fluid and stimulated with the NO donor diethylamine-NONOate (10^–5–10^–3M) or with NO gas (1,000 ppm), which caused concentration-dependent increases in CGRP release up to 166.8%. Second, meningeal blood flow was recorded in vivo in the exposed dura mater using laser Doppler flowmetry. Topical application of the NO donors NONOate, S-nitroso-N-acetylpenicillamine and N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethenamine (10^–5–10^–3M) caused concentration-dependent increases in blood flow. These increases were significantly reduced by local preliminary application of the CGRP receptor antagonist CGRP_8–37 (10^–4M). We conclude that NO stimulates the release of CGRP from dural afferents. The blood-flow-increasing effect of NO seems to be partly mediated by CGRP. The interaction of NO and CGRP may be relevant for the development of vascular headaches.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Increased levels of CGRP have been measured during spontaneous and experimentally induced attacks of migraine and cluster headache [27, 28, 29, 30, 31]. In animal experiments, CGRP is released from meningeal structures by electrical stimulation of the trigeminal ganglion and the dura mater in vivo and in vitro [32, 33]. …”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

2002

View full text Add to dashboard Cite

show abstract

“…Data from literature suggest that CGRP is an important long-lasting migraine mediator (Ebersberger et al, 1999;Lassen et al, 2002;Meng et al, 2007). Therefore, we exposed the primary mixed wild-type TG cultures to BK alone or together with the CGRP receptor antagonist, CGRP 8-37 for 24 h, and subsequently recorded ADP-and UTP-induced increases in [Ca 2ϩ ] i in SGCs (Fig.…”

Section: Cgrp Released From Tg Neurons Upon Bk Application Is Responsmentioning

confidence: 99%

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Ceruti¹,

Villa²,

Fumagalli³

et al. 2011

J. Neurosci.

114

131

View full text Add to dashboard Cite

Within the trigeminal ganglion, crosstalk between neurons and satellite glial cells (SGCs) contributes to neuronal sensitization and transduction of painful stimuli, including migraine pain, at least partly through activation of purinergic receptor mechanisms. We previously showed that the algogenic mediator bradykinin (BK) potentiates purinergic P2Y receptors on SGCs in primary trigeminal cultures. Our present study investigated the molecular basis of this effect in wild-type (WT) mice and Ca V 2.1 ␣1 R192Q mutant knock-in (KI) mice expressing a human mutation causing familial hemiplegic migraine type 1. Single-cell calcium imaging of WT cultures revealed functional BK receptors in neurons only, suggesting a paracrine action by BK to release a soluble mediator responsible for its effects on SGCs. We identified this mediator as the neuropeptide calcitonin gene-related peptide (CGRP), whose levels were markedly increased by BK, while the CGRP antagonist CGRP 8-37 and the anti-migraine drug sumatriptan inhibited BK actions. Unlike CGRP, BK was ineffective in neuron-free SGC cultures, confirming the CGRP neuronal source. P2Y receptor potentiation induced by CGRP in SGCs was mediated via activation of the extracellular signal-regulated kinase 1/2 pathways, and after exposure to CGRP, a significant release of several cytokines was detected. Interestingly, both basal and BK-stimulated CGRP release was higher in KI mouse cultures, where BK significantly upregulated the number of SGCs showing functional UTP-sensitive P2Y receptors. Our findings suggest that P2Y receptors on glial cells might be considered as novel players in the cellular processes underlying migraine pathophysiology and might represent new targets for the development of innovative therapeutic agents against migraine pain.

show abstract

“…The activation of the primary nociceptive trigeminal afferents leads to peripheral neuropeptide release, calcitonin gene-related peptide (CGRP), neurokinin A and substance P are liberated to the perineural space [71,72], leading to vasodilatation and plasma protein extravasation and to the activation of mast cells and leukocytes collectively termed as neurogenic inflammation [73]. These phenomena are well characterized in animals, however in humans only little direct evidence supports the actual presence of neurogenic inflammation during the attack [74].…”

Section: Headache Phase and Postdromementioning

confidence: 99%

Tryptophan Catabolites and Migraine

Bohár

Párdutz

Vécsei

2016

CPD

View full text Add to dashboard Cite

Abstract:Migraine is a highly disabling neurological condition affecting around 15% of the population worldwide.Decades of intensive research shed some light on diseases pathomechanism, but information is still missing about the initiation of the attack. In the past century, serotonin emerged as the main target of both basic and therapeutic research. As a result, the triptans, the only approved migraine specific drugs were developed. The involvement of glutamatergic mechanism in migraine headache development such as cortical hyperexcitability, and cortical spreading depression as the pathological correlate of migraine aura called the attention to the kynurenine pathway in migraine pathomechanism. The serotonin and kynurenine pathways are closely connected, as they both are the metabolic routes of the amino acid tryptophan. Kynurenine catabolites are important participants in glutamatergic neurotransmission, regulation also nociceptive processing of the trigeminal system. The current work attempts to collect recent data on both serotonin and kynurenine research related to migraine and emphasizes the importance of further research on this topic.

show abstract

Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro

Cited by 185 publications

References 56 publications

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Tryptophan Catabolites and Migraine

Contact Info

Product

Resources

About

Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro

Cited by 185 publications

References 56 publications

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Cav2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Tryptophan Catabolites and Migraine

Contact Info

Product

Resources

About

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain