Delayed-type hypersensitivity-induced increase in vascular permeability in the mouse small intestine: inhibition by depletion of sensory neuropeptides and NK1 receptor blockade

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Abstract
1 This study investigates the effects of capsaicin-induced depletion of sensory neuropeptides and of neurokinin! (NK1) receptor blockade on delayed-type hypersensitivity (DTH)-induced changes of vascular permeability in the small intestine of the mouse. 2 The DTH reaction in the small intestine was elicited by dinitrofluorobenzene (DNFB)-contact sensitization followed by oral dinitrobenzene sulphonic acid (DNBS) challenge. To assess vascular leakage the accumulation of the plasma marker, Evans blue (EB), was measured 2, 24 and 48 h after the challenge. 3 The small intestinal DTH reaction was characterized by a significant increase in vascular permeability 24 h after the challenge of previously sensitized mice when compared to vehicle-sensitized mice (P−1 dry weight; vehicle/DTH 207.8 ±25.1 ngEB mg−l dry weight; capsaicin/control: 65.8 ± 11.9 ng EB mg−1 dry weight; capsaicin/ DTH: 84.3 ± 7.6 ng EB mg−1 dry weight. 4 The tachykinins, substance P and neurokinin A (1.5 to 50 × 10−11 mol per mouse, i.v.), induced an increase in vascular leakage in the small intestine of naive mice. The specific NK1 receptor antagonist, RP67580 (10−9 mol per mouse, i.v.) was the most effective in reducing the substance P-induced plasma extravasation when compared with other NK receptor antagonists, FK224 and FK888. 5 Treatment of DNFB-sensitized mice with RP67580 (10−9 mol per mouse, i.v.) immediately before and 1 h after the DNBS challenge resulted in a significant reduction of the DTH-induced increase in vascular permeability at 24h (vehicle/control: 107.5 ±8.8 ng EB mg−1 dry weight; RP67580/control: 95.4±5.4ng EB mg−1 dry weight; vehicle/DTH: 206.6± 22.6ng EB mg−1 dry weight; RP67580/DTH: 132.6±13.6 ng EB mg−1 dry weight, P1 receptors could play an important role in the initiation of the DTH-induced changes in vascular leakage.