title: Topical cholecystokinin depresses itch-associated scratching behavior in mice.
abstract: Cholecystokinin (CCK) serves as a gastrointestinal hormone and also functions as a neuropeptide in the central nervous system (CNS). CCK may be a downregulator in the CNS, as represented by its anti-opioid properties. The existence of CCK in the peripheral nervous system has also been reported. We investigated the suppressive effects of various CCKs on peripheral pruritus in mice. The clipped backs of ICR mice were painted with CCK synthetic peptides and injected intradermally with substance P (SP). The frequency of SP-induced scratching was reduced significantly by topical application of sulfated CCK8 (CCK8S) and CCK7 (CCK7S), but not by nonsulfated CCK8, CCK7, or CCK6. Dermal injection of CCK8S also suppressed the scratching frequency, suggesting that dermal cells as well as epidermal keratinocytes (KCs) are the targets of CCKs. As determined using 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 in ICR mouse KCs. 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 may exert an antipruritic effect via mast cells and that topical CCK may be clinically useful for pruritic skin disorders.
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Fukamachi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mori
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sakabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Shiraishi
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Miwa
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Bito
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D019742:Chemokines, CC; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D043887:Receptor, Cholecystokinin B / Q000235:genetics; D011949:Receptors, Cholecystokinin / Q000235:genetics; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
chemical_list: C090019:8-sulfocholecystokinin octapeptide; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D002756:Cholagogues and Choleretics; D018377:Neurotransmitter Agents; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013373:Substance P; D002766:Cholecystokinin; D012844:Sincalide; D002118:Calcium