Effect of Compound 48/80 on Toxicity of Histamine and of Serotonin in Mice.

Abstract

This study was concerned with the relative importance of mast cell constituents (histamine, serotonin and heparin) in the lethal effects of compound 48/80 (a synthetic phenyl alkylamine substance). Mice were challenged by the intravenous route with specific sublethal doses of compound 48/80 in mixture with graded amounts of either histamine or serotonin (5-hydroxytryptamine). Under these conditions compound 48/80 had an additive effect on the toxicity of histamine and a synergistic effect on the toxicity of serotonin. Since mice contain relatively small amounts of these amines in their tissues in comparison to the amounts necessary to produce lethal effects in this species, it would appear that the lethal effect of compound 48/80 is distinct from its histamine- and serotonin-releasing effects in the mouse. Heparin will protect mice against otherwise lethal doses of 48/80-histamine, 48/80-serotonin or 48/80 alone, but not against either histamine or serotonin. Since relatively small amounts of heparin were required for the protective effect, it is suggested that the degranulation of mast in response to compound 48/80, which results in the release of hlstamine, serotonin and heparin, is essentially a protective response of the tissues to a noxious agent.