Characterizations of sphingosylphosphorylcholine-induced scratching responses in ICR mice using naltrexon, capsaicin, ketotifen and Y-27632.
Sphingosylphosphorylcholine (SPC) is upregulated in the stratum corneum of atopic dermatitis patients by sphingomyelin deacylase. We conducted an investigation, both to confirm that intradermal injection of SPC elicits scratching in mice, and to elucidate the detailed mechanism of the SPC-induced itch-scratch response. Intradermal administration of SPC increased the incidence of scratching behavior in a dose-dependent manner. SPC-induced scratching could be suppressed, significantly, by the mu-opoid receptor antagonist, naltrexon, the vaniloid receptor agonist, capsaicin, and the histamine H1 receptor antagonist ketotifen. d-erythro SPC, one of the SPC stereotypes, could elicit the scratch response, but not l-threo SPC. Y-27632 (1 mg/kg, an inhibitor of Rho-associated protein kinase (ROCK)), was found to suppress SPC-induced scratching. Both the stereospecificity of SPC and the involvement of the Rho/ROCK pathway suggested that SPC-induced scratching is related to the receptor.
Kim
Hyoung June
HJ
AmorePacific Corporation R & D Center, Yongin-shi, Gyeonggi-do 449-729, South Korea.
Kim
Hyuk
H
Han
Eun-Sil
ES
Park
Sun-Mi
SM
Koh
Jae-Young
JY
Kim
Kwang-Mi
KM
Noh
Min-Soo
MS
Kim
Jung-Ju
JJ
Lee
Chang-Hoon
CH
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007271:Injections, Intradermal; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D011725:Pyridines / Q000494:pharmacology*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
D000577:Amides; D000982:Antipruritics; D009125:Muscle Relaxants, Central; D009292:Narcotic Antagonists; D011725:Pyridines; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; C108830:Y 27632; D009271:Naltrexone; D054460:rho-Associated Kinases; D013110:Sphingosine; D002211:Capsaicin; D007665:Ketotifen