Effect of inhibitors of prostaglandin synthesis and prostaglandins E2 and F2alpha on the immunologic release of mediators of inflammation from actively sensitized guinea-pig lung.
Histamine and slow reacting substance of anaphylaxis (SRS-A) were released from actively sensitized guinea-pig chopped lung fragments (100 mg) in a concentration dependent manner by 0.2 to 100 microgram/ml of antigen. Individual variation between lungs in the proportion of the total histamine released by antigen (20 microgram/ml) showed a normal frequency distribution (n = 95). The effect of inhibitors of prostaglandin (PG) synthesis on the release of histamine and SRS-A was examined. Indomethacin (0.03--13 micrometer), racemic 6-chloro-alpha-methylcarbazole-2-acetic acid (0.03--3 micrometer) and sodium salicylate (0.8--8 micrometer) stimulated histamine release by high concentrations of antigen (more than 10 microgram/ml) but had no effect at low concentrations of antigen. These agents stimulated the release of SRS-A at all antigen concentrations tested. In contrast, 5,8,11,14-eicosatetraynoic acid (0.04--42 micrometer) had no effect on the release of histamine but inhibited the release of SRS-A. Histamine release was stimulated by exogenous PGF2alpha (0.01--1 micrometer) in lungs which had control releases in the 25th percentile of the frequency distribution, but was unaffected by exogenous PGE2 (0.01--10 micrometer). In the presence of blockade of PG synthesis by indomethacin (13 micrometer), the stimulatory effect of PGF2alpha was enhanced while PGE2 antagonized the stimulatory effect of indomethacin. These results suggest that 1) histamine and SRS-A release from guinea-pig lung is regulated in part by the de novo synthesis of prostaglandins and 2) that SRS-A synthesis and release is influenced by a metabolite of arachidonic acid produced by a metabolic pathway other than cyclooxygenase.
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism*; D012980:Sodium Salicylate / Q000494:pharmacology
D002227:Carbazoles; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013189:SRS-A; D006632:Histamine; D012980:Sodium Salicylate; D007213:Indomethacin