CELLULAR PATHWAYS OF MAST CELL-SENSITIVE AND CAPSAICIN-SENSITIVE NERVE-EVOKED ILEAL SUBMUCOSAL ARTERIOLAR DILATIONS

This study characterized mast cell- and capsaicin-sensitive sensory ne rve vasodilator mechanisms regulating submucosal arterioles in the gui nea pig ileum. The outside diameter of arterioles in in vitro submucos al preparations from milk-sensitized guinea pigs was monitored using v ideomicroscopy. Superfusion of the cow's milk protein, beta-lactoglobu lin (beta-Lg; 5 mu M), evoked large dilations, which became completely desensitized. beta-Lg-evoked dilations were blocked by pyrilamine or N-G-monomethyl-L-arginine plus indomethacin but not by TTX Electron mi croscopic studies revealed that mast cells, in preparations receiving beta-Lg, demonstrated significant reductions of the dispersed and inta ct granule areas compared with preparations not exposed to beta-Lg. Pa ired experiments were conducted to determine if capsaicin-sensitive, n erve-evoked responses involved mast: cell degranulation. One preparati on received capsaicin (200 nM) followed by beta-Lg (5 mu M); the other preparation received the drugs in reverse order. Prior treatment with capsaicin or beta-Lg had no effect on subsequent dilations evoked by the alternate treatment. Electron microscopy showed that nerve-arterio le associations were 10 times closer than nerve-mast cell associations . Mast cell numbers were not increased by milk sensitization. These fi ndings suggest that mast cell- and capsaicin-sensitive nerve-evoked va sodilator mechanisms act independently in a model in which mast cell n umbers are not increased.