Analysis of the mechanism of histamine release induced by substance P.
Substance P causes release of histamine from rat peritoneal mast cells; the structure-activity relationship shows that N-terminal residue is essential and the hydrophobic region of C-terminal plays an important role. Electrical conductivity of black lipid membrane containing phosphatidic acid was augmented by substance P. In this case, N-terminal residues and C-terminal hydrophobicity were also unavoidable. The partitioning of substance P into the organic phase increased in the presence of phosphatidic acid. The CD spectrum of substance P was changed from the unordered form to beta-form by coexistence of phosphatidic acid/PC liposomes in the medium. The addition of calcium or magnesium in the test solution is effective to prevent either of these phenomena. These findings indicate that substance P probably binds to negatively charged sites of membrane lipids, and subsequent penetration of C-terminal into the hydrophobic core of lipid bilayer may induce an increase of membrane permeability and the following histamine release.
H
H
Shibata
M
M
Mio
K
K
Tasaka
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004553:Electric Conductivity; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D010712:Phosphatidic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*
D008051:Lipid Bilayers; D010712:Phosphatidic Acids; D013373:Substance P; D008274:Magnesium; D002118:Calcium