Organophosphate-induced histamine release from mast cells. 1986

H H Newball, and M A Donlon, and L R Procell, and E A Helgeson, and D R Franz

To examine the hypothesis that soman intoxication leads to degranulation of mast cells with the release of histamine, we studied the effects of soman on rat peritoneal mast cells (RPMC) in vitro and in vivo. In vitro studies were performed with RPMC harvested from Edgewood rats, and challenged with soman (10(-8)-3 X 10(-3) M) in Tyrode's buffer. The RPMC exhibited a dose-dependent release of histamine, with maximal release of 50% at 3 to 6 X 10(-4) M. The release process is an active, secretory, noncytotoxic event, which is calcium and temperature dependent, requires metabolic energy and is influenced by intracellular levels of cyclic AMP. We next studied the in vivo effects of disodium cromoglycate (DSCG, 10(-4) M) on soman and Compound 48/80-induced histamine release. In vivo studies were performed by the i.p. injection of 5 ml of Tyrode's buffer containing soman (O-1 LD50), or Compound 48/80 as a positive control, with or without DSCG. The fluid recovered after approximately 10 min in the peritoneal cavity was examined for percentage of histamine release. In vivo, Compound 48/80 induced 49 +/- 1% histamine release, with no inhibition by DSCG (Compound 48/80 plus DSCG induced 49 +/- 0.4% histamine release). On the other hand, soman (1 LD50) induced 17 +/- 5% extracellular histamine release, with complete inhibition by DSCG (soman plus DSCG induced 3 +/- 1% histamine release). The data indicate that soman induced a dose-dependent release of histamine from RPMC, and provide evidence that histamine is a potentially important mediator of the pathophysiological response to organophosphate intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007531 Isoflurophate A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM. DFP,Diisopropylfluorophosphate,Fluostigmine,Bis(1-methylethyl) Phosphorofluoridate,Di-isopropylphosphorofluoridate,Diisopropylphosphofluoridate,Dyflos,Floropryl,Fluorostigmine,Di isopropylphosphorofluoridate
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008407 Mast Cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR. Basophils, Tissue,Basophil, Tissue,Cell, Mast,Cells, Mast,Mast Cell,Tissue Basophil,Tissue Basophils
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003189 p-Methoxy-N-methylphenethylamine A potent mast cell degranulator. It is involved in histamine release. Agent 48-80,BW 48-80,Compound 48-80,Preparation 48-80,Agent 48 80,Agent 4880,BW 48 80,BW 4880,Compound 48 80,Compound 4880,Preparation 48 80,Preparation 4880,p Methoxy N methylphenethylamine
D004205 Cromolyn Sodium A chromone complex that acts by inhibiting the release of chemical mediators from sensitized MAST CELLS. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack. Disodium Cromoglycate,Sodium Cromoglycate,Aarane,Bicromat Spray,Cromoglicic Acid,Cromoglycate,Cromoglycic Acid,Cromolyn,FPL-670,Intal,Lomudal,Nalcrom,Nasalcrom,Opticrom,Vicrom,Acid, Cromoglicic,Acid, Cromoglycic,Cromoglycate, Disodium,Cromoglycate, Sodium,FPL 670,FPL670
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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