| Project/Area Number |
22659208
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MORI Tomoko 産業医科大学, 医学部, 助教 (80399203)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,160,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | コレシストキニン / かゆみ / 神経ペプチド / 肥満細胞 / 角化細胞 / 血管内皮細胞 / サブスタンスP / CCK2R / そう痒治療薬 |
|---|
| Research Abstract |
Cholecystokinin(CCK) serves as a gastrointestinal hormone and also functions as a neuropeptide in central nervous system(CNS). CCK may be a downregulator in CNS as represented by its anti-opioid properties. The existence of CCK in peripheral nervous system has also been reported. We investigated the suppressive effects of various CCKs on the peripheral pruritus in mice. ICR mice were painted with CCK synthetic peptides on the clipped back and injected intradermally with substance P(SP) on the same site. The frequency of SP-induced scratch was reduced significantly by topical application of sulfated CCK8(CCK8S) and CCK7(CCK7S), but not by non-sulfated CCK8, CCK7 or CCK6. Dermal injection of CCK8S also depressed the scratch frequency, suggesting that dermal cells as well as epidermal keratinocytes are the targets of CCKs. By real-time PCR, mRNA for CCK2R, one of the two types of CCK receptors, was expressed highly in mouse fetal skin-derived mast cells(FSMCs) and moderately ICR mouse keratinocytes. CCK8S decreased in vitro compound 48/80-promoted degranulation of FSMCs with a transient elevation of the intracellular calcium concentration. These findings suggest that CCK exerts an anti-pruritic effect mainly via mast cells, and topical CCK may be clinically useful for pruritic skin disorders.
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