Evidence for the role of neurogenic inflammation components in trypsin‐elicited scratching behaviour in mice

Costa, Robson; Marotta, Denise Mollica; Manjavachi, Marianne N.; Fernandes, Elizabeth S.; Lima-Garcia, Juliana F; Paszcuk, Ana Flávia; Quintão, Nara Lins Meira; Juliano, Luiz; Brain, Susan D.; Calixto, João B.

doi:10.1038/bjp.2008.172

Cited by 84 publications

(89 citation statements)

References 44 publications

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“…Moreover, histamine-evoked itch is reduced in TRPV1 KO mice as well as by inhibiting H1 histamine receptor, PLA2, lipoxygenase or TRPV1 [188,213]. The pharmacological blockade or genetic deletion of TRPV1 also inhibited trypsin-evoked itch in mice [133], which implicates the role of TRPV1 in PAR2-coupled pruriceptive signaling. Furthermore, Imamachi et al [214] found that TRPV1 is required for the transmission of histamine induced scratching behavior, but not for serotonin or endothelin-1 (ET-1) induced itch.…”

Section: Contribution Of Neural Trpv1 To Itch Sensation Induced By Vamentioning

confidence: 79%

“…Bradykinin applied to the skin elevates the release of neuropeptides and prostaglandins [130] and was also reported to evoke itch on lesional atopic skin via a histamine independent manner [131]. Of further importance, both B1 and B2 bradykinin receptors were shown to mediate protease and PAR2 activation-evoked scratching in mice [132,133] and bradykinin was found to evoke scratching responses in complete Freund's adjuvant-inflamed skin [134].…”

Section: Inflammatory Mediators As Peripheral Itch Sensitizersmentioning

confidence: 98%

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TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

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Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nervous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that certain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

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Section: Contribution Of Neural Trpv1 To Itch Sensation Induced By Vamentioning

confidence: 79%

Section: Inflammatory Mediators As Peripheral Itch Sensitizersmentioning

confidence: 98%

TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

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“…Each peak in the accurate mass chromatograph was identified by comparing the retention time with those of the FDAA derivatives of corresponding authentic amino acids. Standards of amino acid gave the following retention times in minutes: 5 …”

Section: Determination Of Absolute Configurationmentioning

confidence: 99%

“…It has been reported that PARs closely relate to inflammation, pain and pruritus. [3][4][5] For instance, injections of proteases are known to cause hyperalgesia through PAR2 in response to both thermal and mechanical stimuli, and injection of trypsin evokes scratching behavior in mice. 5 PAR2 also sensitizes sensory neurons by the transient receptor potential vanilloid 1 (TRPV1)-protein kinase C pathway.…”

Section: Biological Assaysmentioning

confidence: 99%

“…Recently, it was reported that PAR activation closely relates to sensory neuron-associated disorders, such as inflammation, pain and pruritus. [3][4][5] Consequently, inhibitors of PAR signaling, including protease inhibitors, antagonists and intracellular signaling inhibitor, are expected to be therapeutic candidates for these disorders and biological tools.In the screening program for inhibitory compounds of PAR signaling from microbial metabolites, a new antipain analog, antipain Y (Figure 1a), was identified in the culture medium of Streptomyces sp. MJ218-CF4.…”

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confidence: 99%

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Antipain Y, a new antipain analog that inhibits neurotransmitter release from rat dorsal root ganglion neurons

et al. 2009

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Protease-activated receptors (PARs) are a unique class of G proteincoupled receptors activated by proteolytic cleavage of the receptor N terminus. The exposed new N terminus acts as a tethered ligand that interacts with extracellular loop 2 of its receptor, resulting in the initiation of intracellular signaling. To date, four PAR subtypes (PAR1-4) have been reported; these are expressed in a variety of organs and have important functions both physiologically and pathologically. 1,2 Activation of PARs is initiated by several serine proteases. PAR1 is activated by thrombin and PAR2 is activated by several serine proteases, including trypsin and mast cell tryptase. Recently, it was reported that PAR activation closely relates to sensory neuron-associated disorders, such as inflammation, pain and pruritus. [3][4][5] Consequently, inhibitors of PAR signaling, including protease inhibitors, antagonists and intracellular signaling inhibitor, are expected to be therapeutic candidates for these disorders and biological tools.In the screening program for inhibitory compounds of PAR signaling from microbial metabolites, a new antipain analog, antipain Y (Figure 1a), was identified in the culture medium of Streptomyces sp. MJ218-CF4. In this study, we report the isolation, physicochemical properties, structural determination and biological activities of antipain Y. MATERIALS AND METHODS Determination of absolute configurationHydrolysis of antipain Y yielded the corresponding arginine, tyrosine and valine. Each antipain Y and standard amino acid (0.2 mg) was dissolved in 6 M HCl (50 ml), heated at 110 1C for 3 h, and then evaporated to dryness. Each hydrolysate was dissolved in water (50 ml) and treated with 1% Marfey's reagent, 1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA) in a solution of acetone (100 ml) and 7.5% aqueous NaHCO 3 (20 ml) at 40 1C for 1h. After quenching with 3.5 ml of 6 M HCl, the resulting FDAA derivatives were analyzed by reversed-phase liquid chromatography-HR-electrospray ionization-MS. FDAA derivatives were eluted with a linear gradient between (a) CH 3 CN containing 0.01% TFA and (b) 0.01% aqueous TFA from 20 to 50% over 25 min at a flow rate of 0.2 ml min À1 using ODS column (CAPCELL PAK C18MG 5 mm, 2.0 i.d. Â150 mm, Shiseido, Tokyo, Japan). Each peak in the accurate mass chromatograph was identified by comparing the retention time with those of the FDAA derivatives of corresponding authentic amino acids. Biological assaysThe activities of tryptase (Promega, Madison, WI, USA) and trypsin (bovine pancreas trypsin, Worthington Biochemical, Freehold, NJ, USA) were measured by the use of a fluorescent substrate. The assay buffer contained 50 mM tris-HCl (pH 8.0), 120 mM NaCl, 0.02% Triton X-100, 5.8 mM Boc-Phe-Ser-Arg-MCA (Peptide Institute, Osaka, Japan) as a substrate and 15 mg ml À1 tryptase or 1 mg ml À1 trypsin. The reaction was started by adding the substrate, and the reaction mixture was incubated for 30 min at room temperature, the reaction was terminated by adding 20% SDS. The fluorescen...

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Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms

Pall

2009

General, Applied and Systems Toxicology

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Cases of multiple chemical sensitivity (MCS) are initiated by exposure to organic solvents and three classes of pesticides. Each of these can act indirectly to increase NMDA activity and the toxic effects of members of each of these classes can be lowered by using NMDA antagonists. Other chemicals, mercury, H 2 S and CO exposure may also initiate cases of MCS and have toxic responses mediated through increased NMDA activity. Thus each of these types of chemicals appears to act as a toxicant through increased NMDA activity. Six additional types of evidence suggest roles for elevated NMDA activity in MCS, suggesting that this response is involved, not only in MCS case initiation, but also in response to low‐level chemicals in those who are already sensitive. The inference that chemicals act as toxicants in MCS is confirmed by three genetic studies showing that five genes that encode enzymes that metabolize these chemicals act to determine MCS susceptibility. The chronic nature of MCS is thought to be produced by a local biochemical vicious cycle mechanism, the NO/ONOO − cycle, which is initiated by nitric oxide acting through its oxidant product peroxynitrite, which are both produced in MCS in response to excessive NMDA activity. Cycle elements, including NMDA activity, intracellular calcium, nitric oxide and peroxynitrite are thought to interact with other mechanisms, including neural sensitization in the brain and neurogenic inflammation in peripheral tissues to produce the high‐level chemical sensitivity that is the hallmark of MCS. This complex model of MCS is supported by the following types of observations: MCS correlates in the chronic phase of illness, extensive animal model studies implicating almost all NO/ONOO − cycle elements, clinical trial data in the related illnesses chronic fatigue syndrome and fibromyalgia, and a variety of objectively measurable responses to low‐level chemical exposure in MCS patients, responses that should be further studied as possible specific biomarker tests for MCS. While plausible mechanisms are proposed for the generation of both shared and specific symptoms and signs in MCS, there are little data on whether these mechanisms are actually involved in generating these symptoms and signs in MCS. Previous claims that MCS is produced by some sort of psychogenic mechanism have multiple flaws and are inconsistent with the various types of evidence discussed above. Several areas of research are discussed in which the author argues that research will be richly rewarded.

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Evidence for the role of neurogenic inflammation components in trypsin‐elicited scratching behaviour in mice

Cited by 84 publications

References 44 publications

TRP Channels and Pruritus

TRP Channels and Pruritus

Antipain Y, a new antipain analog that inhibits neurotransmitter release from rat dorsal root ganglion neurons

Multiple Chemical Sensitivity: Toxicological Questions and Mechanisms

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