HISTAMINE-POTENTIATING ACTIVITY IN RAT ANAPHYLACTIC PLEURAL FLUID - ROLE OF SEROTONIN

The identity of the histamine-potentiating activity detected in the ra t anaphylactic pleural washing was investigated. Wistar rats of both s exes, weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of ovalbumin and Al(OH)(3) 14 days before allergen chal lenge. In sensitized rats, intrapleural (ipl) injection of ovalbumin ( 12 mu g/cavity) caused an intense protein exudation. A single ipl admi nistration of compound 48/80 (12 mu g/cavity) exhausted the resident m ast cell population and turned the pleural cavity hyporeactive to the allergen challenge performed 5 days later. Allergen-induced exudation occurred in parallel to a dramatic decrease in the amount of cell-stor ed histamine (from 9.6 +/- 1.4 (N = 8) to 1.3 +/- 0.1 (N = 6) mu g/cav ity, P<0.001) in the pleural fluid within 10 min. The anaphylactic cel l-free pleural washing obtained at this time, as well as histamine at a concentration equivalent to that stored in pleural mast cells (10 mu g/cavity), did not induce pleural exudation when injected into normal rats. In contrast, the combined administration of histamine and anaph ylactic pleural washing led to remarkable pleural exudation, comparabl e to that obtained with a high dose of histamine (200 mu g/cavity) alo ne. It is noteworthy that the anaphylactic washing from compound 48/80 -pretreated rats failed to synergize with histamine. Also, synergism w as not reproduced when recipient rats were pretreated with methysergid e (50 mu g/cavity). Consistently, serotonin (5 mu g/cavity) acted syne rgistically with histamine (10 mu g/cavity), producing a greater exuda tive response than observed with the sum of the effects of each vasoac tive amine alone. The results indicate that serotonin accounts for the histamine-potentiating activity noted in the anaphylactic pleural was hing, confirming that the synergistic interaction between these vasoac tive amines plays a critical role in the rat allergic pleurisy.