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

Tryptase and chymase released from activated mast cells degrade the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) to peptide fragments. We have examined whether nedocromil sodium can modulate the ability of rat activated peritoneal mast cells to degrade I-125-CGRP and I-125-VIP. Mast cell-dependent degradation of both I-125-CGRP and I-125-VIP was observed with compound 48/80 (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 inhibition of neuropeptide degradation, with the most effective inhibition observed against anti-IgE-induced degradation of I-125-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bovine trypsin or chymotrypsin to breakdown I-125-VIP. These results suggest that nedocromil sodium inhibits mast cell-dependent degradation of neuropeptides, such as VIP, as a secondary consequence of inhibiting the release of mast cell proteases.