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 125I-CGRP and 125I-VIP. Mast cell-dependent degradation of both 125I-CGRP and 125I-VIP was observed with compound 48/80 (0.03-1 microgram/ml) and in the case of 125I-VIP with anti-IgE (1-20 micrograms/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 125I-VIP. Nedocromil sodium had no inhibitory effect on the ability of lysed mast cells, bovine trypsin or chymotrypsin to breakdown 125I-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.
Biomedical Sciences Division, King's College Chelsea Campus, London, UK.
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Wilsoncroft
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Gaffen
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Reynia
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D053818:Chymases; D010450:Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology*; D017835:Nedocromil; D010529:Peritoneal Cavity / Q000166:cytology; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000187:drug effects; D053802:Tryptases; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D015363:Quinolones; D017835:Nedocromil; D014660:Vasoactive Intestinal Peptide; D010450:Endopeptidases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; D015740:Calcitonin Gene-Related Peptide