title: Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice.
abstract: It has been shown previously that norbinaltorphimine (norBNI) and 5'-guanidinonaltrindole (5'-GNTI), long-acting kappa opioid receptor (KOPR) antagonists, cause frenzied scratching in mice [1,2]. In the current study, we examined if zyklophin, a short-acting cyclic peptide KOPR antagonist, also elicited scratching behavior. When injected s.c. in the nape of the neck of male Swiss-Webster mice, zyklophin at doses of 0.1, 0.3 and 1mg/kg induced dose-related hindleg scratching of the neck between 3 and 15 min after injection. Pretreating mice with norBNI (20mg/kg, i.p.) at 18-20 h before challenge with zyklophin (0.3mg/kg) did not markedly affect scratching. Additionally, KOPR-/- mice given 0.3mg/kg of zyklophin displayed similar levels of scratching as wild-type animals. The absence of KOPR in KOPR-/- mice was confirmed with ex vivo radioligand binding using [(3)H]U69,593. Taken together, our data suggest that the presence of kappa receptors is not required for the excessive scratching caused by zyklophin. Thus, zyklophin, similar to the structurally different KOPR antagonist 5'-GNTI, appears to act at other targets to elicit scratching and potentially the sensation of itch.
authors: Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: kelly.dimattio@temple.edu.
authors: K M
authors: KM
authors: Dimattio
authors: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA. Electronic address: tyakovl@ku.edu.
authors: T V
authors: TV
authors: Yakovleva
authors: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA. Electronic address: jaldrich@ku.edu.
authors: J V
authors: JV
authors: Aldrich
authors: Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: acowan@temple.edu.
authors: A
authors: A
authors: Cowan
authors: Center for Substance Abuse Research and Department of Pharmacology, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: lliuche@temple.edu.
authors: L Y
authors: LY
authors: Liu-Chen
mesh_terms: D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000008:administration & dosage / Q000009:adverse effects*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects*; D011537:Pruritus / Q000139:chemically induced*; D011759:Pyrrolidines / Q000494:pharmacology; D011869:Radioligand Assay; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D044482:Benzeneacetamides; D010446:Peptide Fragments; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C502814:dynorphin A-(1-11)-NH2, Nalpha-benzylTyr(1)-cyclo(Asp(5)-Dap(8))-; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; C045444:U 69593
keywords: Itch; Kappa opioid receptor; Kappa opioid receptor antagonist; Scratching; Zyklophin