Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly- l-arginine in rats

We investigated whether the polycation poly- l-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly- l-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly- l-arginine (50 μg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK 1 receptor antagonist LY303870, ( R)-1-[ N-(2-methoxybenzyl)acetylamino]-3-(1 H-indol-3-yl)-2-[ N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly- l-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly- l-arginine (200 μg/site)-induced scratching. Moreover, poly- l-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly- l-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.