The chemical mediators involved in the pathogenesis of immediate-type hypersensitivity have been the subject of extensive investigations. Immediate-type 1 hypersensitivity reactions are characterized by the immunologically-induced release of histamine, serotonin, prostaglandins and SRS-A. In the present investigation the effect of various drugs on anaphylactic release of histamine, serotonin and heparin from passively sensitized guinea pig lung tissue was studied.
Male white rabbits weighing 2.7-3.0Kg were sensitized with ovalbumin (O-Alb) and gamma globulin was prepared from their peripheral sera by the salting out method. The lung tissue from male Hartley strain guinea pig was minced into fragments (30-50mg). The lung fragments were divided into 0.5 or 1.0g of replicates, and were incubated in gamma globulin solution at 37°C for 3-4 hours saturated with oxygen and carbon dioxide (95:5, v/v). Histamine, serotonin and heparin released from lung fragments by challenging with O-Alb were measured by the methods of OPT, ninhydrin and Azure-A, respectively.
1) The release of histamine, serotonin and heparin was increased dose-dependently by increasing the dose of O-Alb.
2) The release of histamine, serotonin and heparin was inhibited by preincubating with isoproterenol, prostaglandin E
2, 6-keto PGF
1α, disodium cromoglycate, cyclic AMP and verapamil, while it was accelerated by preincubating with thromboxane B
2 and dibutyryl cyclic GMP.
3) The release of histamine, serotonin and heparin showed a tendency to decrease after preincubation with tranexamic acid.
4) There was no correlation between the wet lung tissue weight and the concentration of 6-keto PGF
1α or thromboxane B
2 in the incubation medium after O-Alb challenge.
5) The release of heparin correlated highly with that of histamine and serotonin.
The above results suggest that the release of heparin may play an important role in the release mechanism of various chemical mediators.
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