The mast cell response to substance P: effects of neuraminidase, limulin, and some novel synthetic peptide antagonists.
We have investigated certain aspects of the mechanism whereby substance P triggers secretion of 5-hydroxytryptamine (5-HT) from rat peritoneal mast cells in vitro. Substance P-induced release of 5-HT was inhibited following pretreatment of rat peritoneal cells with 0.01-1.0 units/ml neuraminidase; secretion induced by anti-IgE antibody was inhibited by pretreatment with 1.0 units/ml but not by lower concentrations of enzyme. Addition of the sialic acid-rich substances N-acetyl-neuraminlactose (up to 1.0 mM) and mucin (up to 1.0 mg/ml) to substance P in free solution failed to block the activity of the neuropeptide. Limulin, a sialic acid-specific lectin, failed to block substance P-induced secretion of 5-HT, but was found to possess intrinsic non-lytic secretory activity (at 5-20 micrograms/ml). Release of 5-HT induced by limulin was independent of that induced by substance P. A range of octapeptides incorporating the C-terminal sequence Gly-Ser-Phe-Phe, but differing in degree of cationicity and positioning of cationic residues in the four N-terminal positions, were tested for their capacity to antagonise the mast cell-triggering activity of substance P. A peptide incorporating two lysine residues at the N-terminus was found to have partial substance P antagonist activity; no effects on IgE-mediated secretion were observed.
D000818:Animals; D002097:C-Reactive Protein / Q000494:pharmacology; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009439:Neuraminidase / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D037102:Lectins; C015323:limulin; D012701:Serotonin; D013373:Substance P; D002097:C-Reactive Protein; D009439:Neuraminidase