SUBSTANCE-P ENHANCES ELECTRICAL-FIELD STIMULATION-INDUCED MAST-CELL DEGRANULATION IN RAT TRACHEA

We previously demonstrated in an ex vivo rat tracheal model that chymo tryptic activity is an index of mast cell degranulation and that subst ance P (SP) and electrical field stimulation (EFS) synergistically deg ranulate mucosal and connective tissue mast cells. In the current stud y, we found that the facilitatory effect of SP was apparent at concent rations as-low as 10(-9) M. This effect was mimicked by 10(-7) M neuro kinin A or by 10(-6) M capsaicin and was blocked by the NK1 receptor a ntagonist CP-96,345. SP + EFS-induced mast cell secretion was signific antly attenuated by 10(-6) M tetrodetoxin. The response was also atten uated in tracheas from rats in which sensory nerves had been depleted by systemic pretreatment with capsaicin or in which sympathetic nerves had been depleted by systemic pretreatment with 6-hydroxydopamine. At ropine (10(-6) M) or indomethacin (10(-5) M) also attenuated SP + EFS- induced mast cell secretion. Our findings suggest the importance of a sensitizing rather than a direct stimulating effect of SP on mast cell degranulation. SP may increase the sensitivity of mast cells to EFS-d ischarged mediators or facilitate the release of mast cell-stimulating mediators from autonomic nerves.