Biomaterial Database

The mechanism of basophil histamine release induced by pepstatin A. 1984

G Marone, and M Columbo, and L Soppelsa, and M Condorelli

Pepstatin A, a natural pentapeptide isolated from cultures of actinomycetes, induced histamine secretion from human basophils in the concentration range of 3 X 10(-7) to 10(-4) M. The characteristics of this reaction were similar to those of f-met-peptide-induced histamine release: pepstatin A-induced release required Ca2+, and the release reaction was complete within 2 min at 22 or 37 degrees C but did not occur at 4 degrees C. There was excellent correlation (r = 0.93; p less than 0.001) between the maximal histamine release induced by pepstatin A and f-met-peptide, but there was no relationship to the capacity of basophils to release with anti-IgE (r = -0.03) or the Ca2+ ionophore A23187 (r = -0.22). Release by pepstatin A was reversibly inhibited by two nonreleasing analogs of f-met-peptide, CBZ-Phe-Met and BOC-Met-Leu-Phe. BOC-Met-Leu-Phe competitively inhibited the effect of both f-met-peptide and pepstatin A on histamine release from basophils. The dissociation constant (Kd) for the BOC-Met-Leu-Phe-receptor complex in both conditions was approximately 10(-6) M. Furthermore, there was complete cross-desensitization between pepstatin A and f-met-peptide, whereas cells desensitized to pepstatin A released normally with anti-IgE and vice versa. A variety of pharmacologic agents had similar effects on both pepstatin A- and f-met-peptide-induced release (e.g., slight inhibition with cyclic AMP-active agents, no enhancement with D2O, and marked enhancement with cytochalasin B). We suggest that the natural pentapeptide pepstatin A induces histamine release from human basophils by activating a cell surface receptor(s) also activated by the synthetic tripeptide f-met-peptide.

UI	MeSH Term	Description	Entries
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009240	N-Formylmethionine Leucyl-Phenylalanine	A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.	F-Met-Leu-Phe,N-Formyl-Methionyl-Leucyl-Phenylalanine,Formylmet-Leu-Phe,Formylmethionyl Peptide,Formylmethionyl-Leucyl-Phenylalanine,Formylmethionylleucylphenylalanine,N-Formylated Peptide,N-formylmethionyl-leucyl-phenylalanine,fMet-Leu-Phe,F Met Leu Phe,Formylmet Leu Phe,Formylmethionyl Leucyl Phenylalanine,Leucyl-Phenylalanine, N-Formylmethionine,N Formyl Methionyl Leucyl Phenylalanine,N Formylated Peptide,N Formylmethionine Leucyl Phenylalanine,N formylmethionyl leucyl phenylalanine,Peptide, Formylmethionyl,Peptide, N-Formylated,fMet Leu Phe
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D010436	Pepstatins	N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
D011458	Prostaglandins E	(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.	PGE
D003429	Cross Reactions	Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.	Cross Reaction,Reaction, Cross,Reactions, Cross
D003888	Desensitization, Immunologic	Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity.	Allergen Immunotherapy,Allergy Shots,Hyposensitization Therapy,Immunotherapy, Allergen,Venom Immunotherapy,Immunologic Desensitization,Therapy, Hyposensitization,Allergen Immunotherapies,Allergy Shot,Desensitizations, Immunologic,Hyposensitization Therapies,Immunologic Desensitizations,Immunotherapy, Venom,Shot, Allergy,Venom Immunotherapies
D003994	Bucladesine	A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)	Dibutyryl Adenosine-3',5'-Monophosphate,Dibutyryl Cyclic AMP,(But)(2) cAMP,Bucladesine, Barium (1:1) Salt,Bucladesine, Disodium Salt,Bucladesine, Monosodium Salt,Bucladesine, Sodium Salt,DBcAMP,Dibutyryl Adenosine 3,5 Monophosphate,N',O'-Dibutyryl-cAMP,N(6),0(2')-Dibutyryl Cyclic AMP,AMP, Dibutyryl Cyclic,Adenosine-3',5'-Monophosphate, Dibutyryl,Cyclic AMP, Dibutyryl,Dibutyryl Adenosine 3',5' Monophosphate,Disodium Salt Bucladesine,Monosodium Salt Bucladesine,N',O' Dibutyryl cAMP,Sodium Salt Bucladesine
D004306	Dose-Response Relationship, Immunologic	A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.	Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D006636	Histamine Release	The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects.	Histamine Liberation,Histamine Liberations,Histamine Releases