Repeated challenge with dinitrobenzene sulphonic acid in dinitrofluorobenzene-sensitized mice results in vascular hyperpermeability in the trachea: a role for tachykinins.
1. This study investigates the role of tachykinins in a repeated challenge with dinitrobenzene sulphonic acid (DNS) on the tracheal vascular permeability in dinitrofluorobenzene (DNFB)-sensitized mice. 2. DNFB-contact sensitization was followed by an intranasal (i.n.) challenge with DNS. A second challenge with DNS was administered 24 h after the first challenge. To assess changes in tracheal vascular permeability, Evans blue dye accumulation in tracheal tissue was measured. 3. A repeated challenge with DNS in DNFB-sensitized mice led to a 2.8 fold increase in tracheal vascular permeability when compared to DNFB-sensitized and vehicle-challenged mice or a 2.5 fold increase when compared to DNFB-sensitized single DNS-challenged mice (P<0.001, ANOVA). 4. RP67580 (10-9 mol mouse-1 i.v.) reduced the increased tracheal vascular permeability induced by a second exposure to DNS in DNFB-sensitized mice completely when injected 15 min before the second challenge (P<0.001, ANOVA). 5. The increased tracheal vascular permeability response induced by the second exposure to DNS could be mimicked with i.n. application of capsaicin (10-10 mol mouse-1) or substance P (SP) (10-12 mol mouse-1) to DNFB-sensitized and single DNS-challenged mice. 6. These results suggest that both tachykinin NK1 receptors and sensory nerves are involved in the development of vascular hyperpermeability changes found in the trachea of DNFB-sensitized mice after a repeated DNS-challenge.
van Houwelingen
A
A
Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
van der Avoort
L A
LA
Heuven-Nolsen
D
D
Kraneveld
A D
AD
Nijkamp
F P
FP
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006968:Hypersensitivity, Delayed / Q000378:metabolism / Q000473:pathology*; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D001557:Benzenesulfonates; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D015320:Tachykinins; C007488:dinitrobenzenesulfonic acid; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D004139:Dinitrofluorobenzene; D002211:Capsaicin