title: Structure-activity relationship in the mast cell degranulating capacity of neurotensin fragments.
abstract: The mast cell degranulating capacity of neurotensin and three of its fragments was examined. In Tyrode solution (137 mM NaCl, 2.7 mM KCl, 0.4 mM NaH2PO4, 1.4 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, 5.6 mM glucose, pH 7.4), neither intact neurotensin nor its C-terminal tripeptide (Tyr-Ile-Leu) caused any release of histamine. Concentrations of neurotensin exceeding 10(-4)M did cause histamine release but through lysis of the cells. The C-terminal hexa- and octapeptides of neurotensin (Arg-Arg-Pro-Tyr-Ile-Leu and Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, respectively) induced a non-cytolytic release of histamine with the latter peptide being more active (ED50 = 90 microM for the hexapeptide and 13 microM for the octapeptide). This release was not affected by the C-terminal tripeptide. It was found to be calcium-dependent and was inhibited by the anti-allergic drug, disodium cromoglycate. Phosphatidylserine did not enhance release of histamine and saturation of the immunoglobulin E (IgE) receptors did not inhibit it.
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D003594:Cytoplasmic Granules / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000648:ultrastructure*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D010446:Peptide Fragments; D010718:Phosphatidylserines; D007073:Immunoglobulin E; D009496:Neurotensin; D007770:L-Lactate Dehydrogenase; D002118:Calcium