Document Detail


The effects of NK1 receptor antagonists (FK224 and FK888) on agonist- and antigen-induced nasal microvascular leakage in guinea pigs.
MedLine Citation:
PMID:  9117514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To study the inhibitory effects of two NK1 receptor antagonists on substance P (SP) and antigen-induced increase of nasal vascular permeability in ovalbumen (OA)-sensitized guinea pigs. MATERIAL: Male Dunkin-Hartley guinea pigs. TREATMENT: SP (100 mumol/l), FK224 (1-10 mumol/kg) and FK888 (0.2-2 mumol/kg). METHODS: The in vivo model of nasal microvascular leakage was used for nasal allergic challenge in ovalbumin (OA)-sensitized guinea pigs, or nasal stimulation with substance P (SP) in non-sensitized animals. Nasal microvascular leakage was measured by the accumulation of Evans Blue dye after intravenous injection. RESULTS: Following nasal stimulation with SP 100 microM, the concentration of dye in the nasal lavage fluid rapidly increased. NK1 receptor antagonists FK224 (10 mumol/kg i.v.) and FK888 (2 mumol/kg i.v.) inhibited SP-induced microvascular leakage. In OA-sensitized guinea pigs, exudation of dye into nasal lavage fluid was observed soon after topical antigenic stimulation and continued for over 60 min. Both NK1 receptor antagonists inhibited the immediate phase of the antigen-induced microvascular leakage. CONCLUSIONS: We conclude that the immediate change of vascular permeability during the nasal allergic response is mediated by activation of the NK1 receptor in the guinea-pig.
Authors:
H Shirasaki; K Asakura; S Narita; M Watanabe; A Kataura
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inflammation research : official journal of the European Histamine Research Society ... [et al.]     Volume:  46     ISSN:  1023-3830     ISO Abbreviation:  Inflamm. Res.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-04-24     Completed Date:  1997-04-24     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9508160     Medline TA:  Inflamm Res     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  28-31     Citation Subset:  IM    
Affiliation:
Department of Otolaryngology, Sapporo Medical University, School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens / immunology
Capillary Permeability / drug effects*
Dipeptides / pharmacology*
Guinea Pigs
Indoles / pharmacology*
Male
Nose / blood supply*,  drug effects
Ovalbumin / immunology
Peptides, Cyclic / pharmacology*
Receptors, Neurokinin-1 / antagonists & inhibitors*,  physiology
Respiratory Hypersensitivity / immunology
Substance P / pharmacology
Chemical
Reg. No./Substance:
0/Antigens; 0/Dipeptides; 0/Indoles; 0/Peptides, Cyclic; 0/Receptors, Neurokinin-1; 125787-94-2/FK 224; 138449-07-7/FK 888; 33507-63-0/Substance P; 9006-59-1/Ovalbumin

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