Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

Structure-activity studies have been performed on a series of naturally occurring and ‘tailor-made’ polypeptides, by measurement of ability to induce selective histamine release from normal rat peritoneal mast cells in vitro. Compounds investigated include corticotropin and melittin derivatives, mast-cell-degranulating peptide from bee venom, polymyxin B, bradykinin and various synthetic poly(amino acids) and short-chain peptides. It was confirmed that a cluster of four basic residues (lysine or arginine) was optimal for histamine release by corticotropin and melittin polypeptides, provided that the C-terminal carboxyl group was substituted (by, for instance, amidation). In contrast, the presence of a free C-terminal carboxyl group or nearby dicarboxylic acid residues led to a considerable diminution in histamine-releasing activity. Likewise, polypeptides comprised essentially of acidic amino acids were inactive. On the basis of these observations it has been possible to predict that synthetic peptides comprising a particular sequence within the Fc region of human immunoglobulin E, the immunoglobulin class particularly involved in mediation of allergic reactions of the immediate type, would possess potent histamine-releasing activity when similarly made to react with normal rat mast cells. The further study of such a structure should throw new light on the molecular basis of allergen-antibody triggering of mast cells.

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Studies on the Role of Calcium in the Anaphylactic Histamine Release from Isolated Rat Mast Cells

Acta Pharmacologica et Toxicologica ◽

10.1111/j.1600-0773.1974.tb00748.x ◽

2009 ◽

Vol 35 (4) ◽

pp. 284-292 ◽

Cited By ~ 14

Author(s):

Nina Grosman ◽

Bertil Diamant

Keyword(s):

Mast Cells ◽

Histamine Release ◽

Isolated Rat ◽

Anaphylactic Histamine Release ◽

Rat Mast Cells

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Further studies on histamine release from rat mast cells in vitro induced by peptides. Characteristics of a synthetic intermediate with potent releasing activity

Biochemical Journal ◽

10.1042/bj1910233 ◽

1980 ◽

Vol 191 (1) ◽

pp. 233-237 ◽

Cited By ~ 16

Author(s):

P D Roy ◽

D M Moran ◽

V Bryant ◽

R Stevenson ◽

D R Stanworth

Keyword(s):

Mast Cells ◽

Histamine Release ◽

Synthetic Peptide ◽

Structural Basis ◽

Optical Isomers ◽

Compound I ◽

Synthetic Intermediate ◽

Rat Mast Cells ◽

Release Processes

Previous studies on histamine release by corticotropin peptides and melittin peptides were extended, leading to the identification of a synthetic peptide intermediate, Lys(Z)-Arg(NO2)-Arg(NO2)OMe, (I) as an active non-cytolytic histamine releaser from rat mast cells. However, significant differences in the releasing capacity of optical isomers of this compound, and of Lys-Lys-Arg-ArgOMe [methyl ester of corticotropin-(15-18)-tetrapeptide; ‘basic core’] were observed, with the L-forms being markedly more active. A study of various analogues of the tripeptide compound (I) indicated that the structural basis for mast-cell triggering by such peptidic agents was highly specific. The relevance of these observations to the immunologically induced histamine-release processes is discussed.

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