The Effects of the Immunologic Release of Histamine upon Human Lung Cyclic Nucleotide Levels and Prostaglandin Generation

Leslie F. Platshon; Michael Kaliner

doi:10.1172/JCI109230

The Effects of the Immunologic Release of Histamine upon Human Lung Cyclic Nucleotide Levels and Prostaglandin Generation

Leslie F. Platshon and Michael Kaliner

Published December 1, 1978 - More info

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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_2α, 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_2α 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_2α synthesis accompanying anaphylaxis; H-2 antagonists had no effect. Exogenous histamine induced PGF_2α 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_2α was not influenced by antihistamines. Therefore, histamine interactions with human lung result in the synthesis of both PGF_2α and cyclic GMP in response to H-1 stimulation, and of cyclic AMP through H-2 stimulation.