title: The effects of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation.
abstract: The effect of the antigen-induced, immunoglobulin (Ig)E-dependent release of mediators from human lung tissue was analyzed for coincident changes in the tissue levels of cyclic nucleotides. Simultaneously with the appearance of mediators, lung cyclic guanosine 3',5'-monophosphate (GMP) increased from 0.9+/-0.2 to 12.63+/-4.5 pmol/mg protein and cyclic AMP increased threefold from the initial levels of 5.1+/-1.4 pmol/mg protein. The release of histamine and prostaglandin (PG)F(2alpha), as well as the associated increases in cyclic nucleotides, peaked within 10 min of anaphylaxis. Antagonists of histamine's H-1 receptor prevented anaphylaxis-associated increases in cyclic GMP, whereas H-2 antagonists prevented the cyclic AMP response. Neither of these antagonists influenced the pattern or quantity of histamine or slow-reacting substance of anaphylaxis release. Prevention of PGF(2alpha) synthesis with acetylsalicylic acid failed to influence histamine or slow-reacting substance of anaphylaxis release or the concomitant increases in cyclic nucleotides. Histamine, added exogenously, produced a prompt increase in the cyclic AMP and cyclic GMP levels of human lung. As was seen after anaphylaxis, H-1 anatagonists prevented the cyclic GMP response to histamine, whereas H-2 antagonists prevented the cyclic AMP response.H-1 antagonists prevented 50% of the PGF(2alpha) synthesis accompanying anaphylaxis; H-2 antagonists had no effect. Exogenous histamine induced PGF(2alpha) synthesis; this synthesis was prevented by H-1 but not H-2 antagonists, and was reproduced by 2-methylhistamine (H-1 agonist) but not by dimaprit (H-2 agonist). Arachidonic acid generation of PGF(2alpha) was not influenced by antihistamines. Therefore, histamine interactions with human lung result in the synthesis of both PGF(2alpha) and cyclic GMP in response to H-1 stimulation, and of cyclic AMP through H-2 stimulation.
mesh_terms: D000707:Anaphylaxis / Q000276:immunology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism*; D013189:SRS-A / Q000276:immunology / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011460:Prostaglandins F; D013189:SRS-A; D007073:Immunoglobulin E; D000242:Cyclic AMP; D006152:Cyclic GMP; D001241:Aspirin