Characterization of the conjunctival vasopermeability response to leukotrienes and their involvement in immediate hypersensitivity.
The microvascular permeability response of the guinea pig conjunctiva to sulfidopeptide leukotrienes (LTs) was quantified as extravasation of radiolabeled bovine serum albumin. The LTs were potent inducers of increased microvascular permeability, with relative potencies LTE4 greater than or equal to LTD4 greater than LTC4. The response to LTs was unaffected by indomethacin or a pyrilamine/cimetidine combination, but the LT antagonists FPL 55712 and SKF 102922 significantly inhibited the response to LTC4, LTD4 and LTE4. In guinea pigs actively sensitized to ovalbumin, topical ocular administration of ovalbumin markedly increased conjunctival microvascular permeability; this response was reduced by approximately 50% following histaminergic blockade by pyrilamine/cimetidine. FPL 55712 and SKF 102922 and the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) had no effect on the response to antigen when used alone. However, each agent significantly reduced the non-histaminergic component of the response when given in conjunction with pyrilamine/cimetidine. Thus, it appears that the immediate hypersensitivity response in guinea pig conjunctiva has a possible non-histaminergic component which is at least partly mediated by LTs.
Gary
R K
RK
Department of Pharmacology, Allergan Inc., Irvine, CA 92715.
Woodward
D F
DF
Nieves
A L
AL
Williams
L S
LS
Gleason
J G
JG
Wasserman
M A
MA
D000818:Animals; D000941:Antigens / Q000276:immunology; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D003228:Conjunctiva / Q000098:blood supply* / Q000276:immunology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D017999:Leukotriene E4; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D013189:SRS-A / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D013237:Stereoisomerism; D013997:Time Factors
D000941:Antigens; D002867:Chromones; D003998:Dicarboxylic Acids; D013189:SRS-A; D017999:Leukotriene E4; D009637:Masoprocol; C006312:FPL 55712; D010047:Ovalbumin; C046472:5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid