Release of prostaglandins and histamine from sensitized and anaphylactic guinea pig lungs—changes in cyclic AMP levels

Abstract

Healthy control, antigen-sensitized and anaphylactic guinea pig lungs were perfused with Tyrode's solution, and immuno reactive prostaglandins E and F 2α (PGE, PGF 2α), 15-keto-13, 14-dihydro-PGF 2α/E 2 (metabolite) and histamine measured in the outflows. Histamine and cyclic AMP were also determined in the lung tissue. Significantly more PGE, PGF 2α, metabolite and histamine were spontaneously released from sensitized lungs than control lungs. Anaphylaxis further increased the release of these compounds and also raised the tissue levels of cyclic AMP. The largest amounts of PGE and PGF 2α, in the perfusate were found during min 2 and of histamine during min 1 after antigen administration. Pretreatment of the sensitized lungs with indomethacin, di-isopropylfluorophosphate (DFP) and epinephrine blocked the anaphylactic release of mediators. Indomethacin and DFP also reduced the cyclic AMP levels, while epinephrine pretreatment only marginally affected the rise in cyclic AMP induced by anaphylaxis. When given after the antigen, epinephrine had a minimal effect on the release of prostaglandins (PGs) and histamine, but enhanced the effect of anaphylaxis on cyclic AMP. The data indicate that sensitization with antigen may change the biological properties of the organism, as evidenced by the increased outflow of PGs and histamine. The differentiation of the effects of blockers points to an intricate relationship between the release of PGs and histamine and the tissue levels of cyclic AMP in sensitized and anaphylactic lungs.