Itch-Scratch Responses Induced by Lysophosphatidic Acid in Mice

Hashimoto, Terumasa; Ohata, Hisayuki; Momose, Kazutaka

doi:10.1159/000078632

Cited by 69 publications

(54 citation statements)

References 26 publications

(28 reference statements)

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“…2). It was found that, at the same concentration, Gsp elicits scratching to the less extent as histamine, LPA or SPC (Inagaki et al, 2000;Hashimoto et al, 2004;Kim et al, 2008c). Incidentally, the reason that high amounts of Gsp are required to provoke the scratch response in ICR mice might be the weak binding affinity of the putative Gsp receptor in mice or due to nonspecific binding to endogenous proteins such as albumin in mice (Han et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Glucosylsphingosine Induces Itch-Scratch Responses in Mice

Kim¹,

Kim²,

Noh³

et al. 2010

Biomolecules and Therapeutics

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-Pruritus is one of major symptoms in atopic dermatis. The pathophysiological mechanism of pruritus is unclear. The search for pruritogen is important in elucidating the pathophysiological mechanism of pruritus in atopic dermatitis. Glucosylsphingosine (Gsp) is upregulated in the strateum corneum of atopic dermatitis patients. We investigated to determine whether Gsp induces itch-scratch responses (ISRs) in mice. Intradermal administration of Gsp induces ISRs. Gsp dose-dependently induced scratching response at 50-500 nmol/site range. Pretreatment with naltrexone, an opioid μ receptor antagonist, and capsaicin, a TrpV1 receptor agonist, inhibited Gsp-induced ISRs. Additionally, Gsp-induced ISRs were also suppressed by cyproheptadine, an antagonist of serotonin receptor. These findings suggest that Gsp-induced scratching might be at least partly mediated by capsaicin-sensitive primary afferents, and the opioids receptor systems might be involved in transmission of itch signaling in the central nervous system. Furthermore, our findings suggest that Gsp-induced ISRs may be attributable to the serotonin-mediated pathways and Gsp is not any more one of byproducts of abnormal skin barrier but can lead to induce pruritus, one of typical symptoms of atopic dermatitis.

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Section: Discussionmentioning

confidence: 99%

Glucosylsphingosine Induces Itch-Scratch Responses in Mice

Kim¹,

Kim²,

Noh³

et al. 2010

Biomolecules and Therapeutics

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“…Treatments with Ki16425 and LPA started 9 weeks after beginning the feeding protocol. The dose of LPA injected was adapted from previous reports [24,25]. The concentration of Ki16425 used had previously been demonstrated to block LPA receptors in vivo [26].…”

Section: Methodsmentioning

confidence: 99%

Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice

et al. 2013

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Aims/hypothesis Lysophosphatidic acid (LPA) is a lipid mediator produced by adipocytes that acts via specific Gprotein-coupled receptors; its synthesis is modulated in obesity. We previously reported that reducing adipocyte LPA production in high-fat diet (HFD)-fed obese mice is associated with improved glucose tolerance, suggesting a negative impact of LPA on glucose homeostasis. Here, our aim was to test this hypothesis. Methods First, glucose tolerance and plasma insulin were assessed after acute (30 min) injection of LPA (50 mg/kg) or of the LPA1/LPA3 receptor antagonist Ki16425 (5 mgkg −1 day −1 , i.p.) in non-obese mice fed a normal diet (ND) and in obese/prediabetic (defined as glucose-intolerant) HFD mice. Glucose and insulin tolerance, pancreas morphology, glycogen storage, glucose oxidation and glucose transport were then studied after chronic treatment (3 weeks) of HFD mice with Ki16425. Results In ND and HFD mice, LPA acutely impaired glucose tolerance by inhibiting glucose-induced insulin secretion. These effects were blocked by pre-injection of Ki16425 (5 mg/kg, i.p.). Inhibition of glucoseinduced insulin secretion by LPA also occurred in isolated mouse islets. Plasma LPA was higher in HFD mice than in ND mice and Ki16425 transiently improved glucose tolerance. The beneficial effect of Ki16425 became permanent after chronic treatment and was associated with increased pancreatic islet mass and higher fasting insulinaemia. Chronic treatment with Ki16425 also improved insulin tolerance and increased liver glycogen storage and basal glucose use in skeletal muscle. Conclusions/interpretation Exogenous and endogenous LPA exerts a deleterious effect on glucose disposal through a reduction of plasma insulin; pharmacological blockade of LPA receptors improves glucose homeostasis in obese/prediabetic mice.

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“…49) Intradermal injection of lysophosphatidic acid induces scratching in mice. 49,50) Autotaxin activity in the serum is not increased in patients with other pruritic diseases, such as uremia, Hodgkin's disease, or atopic dermatitis. 51) These findings raise the possibility that lysophosphatidic acid and autotaxin are potential therapeutic targets for cholestatic pruritus.…”

Section: Lipid Mediatorsmentioning

confidence: 99%

Potential New Therapeutic Targets for Pathological Pruritus

Kuraishi

2013

Biological & Pharmaceutical Bulletin

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Very few approved medications are indicated for the treatment of pruritus, and drug development for pruritic diseases is awaited. During the past two decades, progress has been made in understanding the molecular basis of the physiology and pathophysiology of pruritus. Newly identified potential targets for pathological pruritus include receptors (histamine H 4 receptor, leukotriene B 4 receptors, interleukin-31 receptor A, bombesin BB 2 receptor, toll-like receptor 3, α-adrenoceptor, and opioid μ-and κ-receptors), channels (transient receptor potential (TRP) V3 and TRPA1 channels), and enzymes (histidine decarboxylase, sphingomyelin glucosylceramide deacylase, 5-lipoxygenase, leukotriene A 4 hydrolase, and autotaxin). The development of specific, effective blockers and agonists/antagonists of these targets is awaited.

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Itch-Scratch Responses Induced by Lysophosphatidic Acid in Mice

Cited by 69 publications

References 26 publications

Glucosylsphingosine Induces Itch-Scratch Responses in Mice

Glucosylsphingosine Induces Itch-Scratch Responses in Mice

Lysophosphatidic acid impairs glucose homeostasis and inhibits insulin secretion in high-fat diet obese mice

Potential New Therapeutic Targets for Pathological Pruritus

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