[Inhibition of chemically induced microvascular leakage by ONO-1078, a leukotriene antagonist, in rat skin].
This study is to determine whether ONO-1078, a potent leukotriene antagonist, influences chemically induced rat skin microvascular leakage which is considered to be, at least in part, due to stimulation of sensory nerve ending and release of sensory neuropeptides. Evans blue dye was used as a tracer for plasma leakage. Intradermal injections of chemical stimuli, histamine (10 micrograms), capsaicin (10 micrograms) and formalin (0.5 mg), evoked Evans blue dye extravasation in rat skin. Intraperitoneal ONO-1078 dose-dependently inhibited the dye extravasation induced by these stimuli, with ID5v values of 1.98 mg.kg-1 for histamine, 1.78 mg.kg-1 for capsaicin, and 2.23 mg.kg-1 for formalin. In contrast to chlorpheniramine, a H1 receptor antagonist, the inhibitory effect of ONO-1078 was weaker on histamine, but more potent on capsaicin and formalin. The inhibitory effect of dexamethasone was more potent than that of ONO-1078 on these stimuli. On the other hand, ONO-1078 inhibited the dye extravasation induced by leukotriene D4 (0.05 micrograms), but showed no effect on those induced by substance P (0.5 micrograms, a sensory neuropeptide), a larger dose of histamine (100 micrograms), and bradykinin (1 microgram). These results suggest that inhibition of chemically induced skin microvascular leakage by ONO-1078 may be mediated by inhibiting the release of sensory neuropeptides from capsaicin-sensitive sensory fibers.
Wei
E Q
EQ
Department of Pharmacology, Zhejiang Medical University, Hangzhou.
Wang
Y C
YC
Xin
X H
XH
Chen
L P
LP
Zhang
L F
LF
Bian
R L
RL
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000037:antagonists & inhibitors; D002744:Chlorpheniramine / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005557:Formaldehyde / Q000037:antagonists & inhibitors; D006633:Histamine Antagonists; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000037:antagonists & inhibitors; D012867:Skin / Q000098:blood supply*
D002867:Chromones; D006633:Histamine Antagonists; D013189:SRS-A; D005557:Formaldehyde; D002744:Chlorpheniramine; D003907:Dexamethasone; D002211:Capsaicin; C047681:pranlukast