Suppression of endotoxin-induced corticosterone secretion in rats by H1-antihistamine

Corticosterone (CS) secretion is stimulated in rats by an intraperitoneal injection of bacterial lipopolysaccharide (LPS) or by subjecting the animals to immobilization stress. LPS injection caused a significant increase in the lung histamine level and a sharp reduction in the number of intact peritoneal mast cells. Injection of compound 48/80, a histamine liberator, provoked an increase in the histamine levels of the blood and lung and a decrease in the number of intact peritoneal mast cells with a concomitant increase in CS secretion. Administration of histamine, at a dose of 10 mg/kg, induced a marked increase in CS release. LPS-induced CS secretion was attenuated by pretreatment with an H1-antihistamine, promethazine (PMZ), whereas an H2-antihistamine, metiamide, had no effect. In contrast, PMZ was ineffective on CS release provoked by immobilization stress. These results suggest that LPS-induced CS release is mediated, in part, by histamine released in the peripheral tissues, whereas an immobilization stress-induced increase is not mediated by the amine.

The Effects of Compound 48/80 on the Fibrinolytic Activity of Dogs

SummaryIt has been demonstrated that histamine by itself, did play some role in the activation mechanism of fibrinolysis. In this particular work, it was demonstrated that histamine at doses not affecting blood pressure levels, did not exert any direct immediate effect on fibrinolytic activity.Compound 48/80, a powerful mast cell depleter and histamine liberator, by itself, has no direct molecular effect on fibrinolytic activity, but rather, through the release of activators and/or inhibitors form mast cells, will exert either an activating or inhibiting action, according to the dose used. Low doses, such as 0.2 mg/kg i. v. will achieve a higher degree of activator release, while doses of 1.0 mg/kg will result in higher inhibitors release from mast cells.