THE MODULATION BY NEDOCROMIL SODIUM OF PROTEASES RELEASED FROM RAT PERITONEAL MAST-CELLS CAPABLE OF DEGRADING VASOACTIVE-INTESTINAL-PEPTIDEAND CALCITONIN-GENE-RELATED PEPTIDE
P. Wilsoncroft et al., THE MODULATION BY NEDOCROMIL SODIUM OF PROTEASES RELEASED FROM RAT PERITONEAL MAST-CELLS CAPABLE OF DEGRADING VASOACTIVE-INTESTINAL-PEPTIDEAND CALCITONIN-GENE-RELATED PEPTIDE, Immunopharmacology, 25(3), 1993, pp. 197-204
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.