THE MODULATION BY NEDOCROMIL SODIUM OF PROTEASES RELEASED FROM RAT PERITONEAL MAST-CELLS CAPABLE OF DEGRADING VASOACTIVE-INTESTINAL-PEPTIDEAND CALCITONIN-GENE-RELATED PEPTIDE

Tryptase and chymase released from activated mast cells degrade the ne uropeptides calcitonin gene-related peptide (CGRP) and vasoactive inte stinal peptide (VIP) to peptide fragments. We have examined whether ne docromil sodium can modulate the ability of rat activated peritoneal m ast cells to degrade I-125-CGRP and I-125-VIP. Mast cell-dependent deg radation of both I-125-CGRP and I-125-VIP was observed with compound 4 8/80 (0.03-1 mug/ml) and in the case of I-125-VIP with anti-IgE (1-20 mug/ml). Nedocromil sodium (10(-6)-10(-4) M) caused significant inhibi tion of neuropeptide degradation, with the most effective inhibition o bserved against anti-IgE-induced degradation of I-125-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bo vine trypsin or chymotrypsin to breakdown I-125-VIP. These results sug gest that nedocromil sodium inhibits mast cell-dependent degradation o f neuropeptides, such as VIP, as a secondary consequence of inhibiting the release of mast cell proteases.