Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Tsujii, Kenichiro; Andoh, Tsugunobu; Ui, Haruna; Lee, Jung‐Bum; Kuraishi, Yasushi

doi:10.1254/jphs.08332fp

Cited by 60 publications

(62 citation statements)

References 31 publications

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“…PAR2 activation by mast-cell tryptase may play an important role in scratching in NC mice with chronic allergic dermatitis. 78,79) …”

Section: Mast-cell Itch Mediatorsmentioning

confidence: 99%

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Kuraishi

2015

Biological & Pharmaceutical Bulletin

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Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was thought to be a key itch mediator. However, histamine and mast-cell degranulation were reported not to elicit scratching in animals. It was difficult to investigate the pathophysiology of itching and to evaluate the antipruritic efficacy of chemical agents in the early 1990 s. We showed that hind-paw scratching and biting were elicited by stimulation with pruritogenic agents in mice. Those results demonstrated for the first time that cutaneous itching could be evaluated behaviorally in animals. We established various animal models of pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell histamine did not play a key role in itching in any animal model examined except for the pollen allergy model. Histamine is not an exclusive itch mediator of mast cells; tryptase and leukotriene B 4 released from mast cells also act as itch mediators. Epidermal keratinocytes release several itch mediators, such as leukotriene B 4 , sphingosylphosphorylcholine, thromboxane A 2 , nociceptin, nitric oxide, and histamine, which may play important roles in pathological itching. Appropriate animal models of pathological itching are needed for pharmacological evaluation of the antipruritic efficacy of chemical agents.

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“…PAR2 activation by mast-cell tryptase may play an important role in scratching in NC mice with chronic allergic dermatitis. 78,79) …”

Section: Mast-cell Itch Mediatorsmentioning

confidence: 99%

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Kuraishi

2015

Biological & Pharmaceutical Bulletin

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“…For atopic dermatitis, tryptase has been proposed to trigger the itch sensation via activating protease-activating receptor 2 (PAR2), a member of the GPCR family [27] . However, a more recent study argues that PAR2 contributes to atopic dermatitis by inducing thymic stromal lymphopoietin (TSLP) release from keratinocytes [28] .…”

Section: Peripheral Mechanisms Of Itch and Painmentioning

confidence: 99%

Molecular Mechanisms of Itch and Pain: An Overview

Lee

2015

Itch Pain

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Itch and pain are two distinct sensory modalities elicited by noxious and pruritic stimuli, respectively. The cellular and electrophysiological characteristics of itch and pain are very similar; thus discerning the mechanical difference between these two sensory modalities has long been elusive. Recent advances in this field have revealed various neuronal receptors responsible for itch and pain signal transduction and transmission. These studies have identified a distinct sub-population of sensory neurons responsible for itch signal transduction. In addition, itch and pain information conveyed to the spinal cord are processed and regulated by distinct spinal cord neurons. Although both itch and pain senses are required for our daily lives, chronic and hyper-sensation of itch and pain results in a debilitating disease state. Studies have now begun to elucidate mechanisms for the sensitization of pain and itch and also to unravel counter-regulatory mechanisms between itch and pain at the spinal cord level. Interestingly, toll-like receptors (TLRs), an innate immune receptor, has been implicated in the central sensitization of both pain and itch. In this review, we will briefly provide an overview of the molecular mechanisms of itch and pain. Additionally, we will discuss the recently uncovered role of TLRs in itch and pain sensation.

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“…DISCUSSION MEGL suppressed the scratching induced by intradermal SLIGRL-NH 2 , a PAR 2 receptor agonist, 16) and 5-HT in mice. The PAR 2 receptor agonist tryptase has been suggested to be involved in pruritus of atopic dermatitis 17,18) and 5-HT is in pruritus of polycythemia vera. 19) Thus, it is interesting to examine the effects of MEGL on these H 1 histamine-receptor antagonist-resistant pruritic diseases.…”

Section: Effects Of Megl On Pruritogen-induced Scratch-mentioning

confidence: 99%

Inhibitory Effect of Methanol Extract of Ganoderma lucidum on Acute Itch-Associated Responses in Mice

Zhang

Andoh

Konno

et al. 2010

Biological & Pharmaceutical Bulletin

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Itch, a skin sensation that provokes the desire to scratch, accompanies various skin diseases such as atopic dermatitis. Although H 1 histamine-receptor antagonists are the drugs of first choice for the treatment of itch, many pruritic diseases except acute urticaria do not show a good response.1) Therefore, it is important to develop new drugs that are effective against antihistamine-resistant pruritus.The fruiting body of Ganoderma lucidum (G. lucidum) KARST has been used as a crude drug in China, Japan, and Korea for the treatment of hypertension, chronic hepatitis, hyperglycemia, cancer, and chronic bronchitis.2,3) The extract of G. lucidum has been shown to have an antiallergic activity, which is mainly due to its inhibitory effect on the histamine release from mast cells. 4,5) Many antiallergic drugs generally show antipruritic activity, 6) but the antipruritic activity of G. lucidum has not yet been elucidated.Scratching, an itch-related response, can be elicited by intradermal injections of various substances, including histamine, 7) substance P, 8,9) 5-hydroxytryptamine (5-HT), 10) proteinase-activated receptor-2 (PAR 2 )-activating peptide, 11) and compound 48/80. 8,12) Scratching induced by these substances may not be mediated by the same primary afferents. 9,[13][14][15] Therefore, in the present study, we examined whether G. lucidum can ameliorate the scratching elicited by the pruritogens mentioned above in order to determine the antipruritic efficacy of G. lucidum and its possible mechanisms. MATERIALS AND METHODS AnimalsMale ICR mice (Japan SLC, Ltd., Shizuoka, Japan) aged 5-8 weeks and weighing 24-26 g were used. They were housed under controlled temperature (23°CϮ 1°C), humidity (60%Ϯ5%), and light (lights on from 8:00-20:00 h). Food and water were freely available. Procedures for animal experiments were approved by the Committee for Animal Experiments at the University of Toyama and were conducted in accordance with the guidelines of the Japanese Pharmacological Society.Agents 5-HT, a-methyl-5-HT, and compound 48/80were purchased from Sigma (St. Louis, MO, U.S.A.). Substance P and histamine were purchased from Peptide Institute, Inc. (Osaka, Japan) and Wako Pure Chemical Industries, Ltd. (Osaka, Japan), respectively. Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SLIGRL-NH 2 ) was synthesized and identified by JBL with a peptide synthesizer PSSM-8 (Shimadzu Co., Kyoto, Japan) and a matrix assisted laser desorption/ionization timeof-flight (MALDI TOF)-MS Autoflex T1 (Bruker Daltonics, Billerica, MA, U.S.A.), respectively. These agents were dissolved in physiological saline and injected intradermally in a volume of 50 ml into the rostral skin of mice, the hair of which was clipped a day before the experiment was conducted. Preparation of the Methanol Extract of G. lucidum (MEGL)The dried powder (1 kg) of G. lucidum (Koshiro Co., Ltd., Kyoto, Japan) was extracted three times with methanol for 3 h and the methanol extract was then dried; the yield of MEGL was 17.8%. MEGL was suspended in 5% gum arabic before use a...

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Involvement of Tryptase and Proteinase-Activated Receptor-2 in Spontaneous Itch-Associated Response in Mice With Atopy-like Dermatitis

Cited by 60 publications

References 31 publications

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Methods for Preclinical Assessment of Antipruritic Agents and Itch Mechanisms Independent of Mast-Cell Histamine

Molecular Mechanisms of Itch and Pain: An Overview

Inhibitory Effect of Methanol Extract of Ganoderma lucidum on Acute Itch-Associated Responses in Mice

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