Synergistic Interactions between Neuropeptide and Histamine on the Capillary Permeability in Rat Skin: Evaluation by Reflectance Spectrophotometry

Effects of neuropeptides on capillary permeability and their interactions with histamine (HIS) in rat skin were investigated. The capillary permeability was measured continuously by reflectance spectrophotometry after intravenous (iv) injection of Evans blue dye. The capillary permeability was increased dose-dependently by the intradermal injection of HIS (0.3–100 μg/site) and substance P (SP; 25–250 ng/site). Calcitonin gene-related peptide (80–800 ng/site) elicited a significant but less increase than did SP. Capsaicin (30 μg/site) also increased capillary permeability slightly but significantly, suggesting the release of endogenous neuropeptides. Both diphenhydramine (DPH; 3 mg/kg, iv) and cimetidine (CIM; 30 mg/kg, iv) reduced HIS-induced responses. DPH also reduced the SP-induced response significantly, but CIM did not. An SP antagonist, [d-Pro2,d-Trp7,9]-SP (1.3 mg/kg, iv), reduced not only SP- but also HIS-induced responses. Furthermore, the HIS-induced response was attenuated by pretreatment with epicutaneous capsaicin for 4 days, depleting endogenous SP. These results delineate the synergistic interactions between SP and HIS in rat skin and suggest the participation of neuropeptides in increasing capillary permeability.