Inhibition of Histamine Release and Formation of Slow Reacting Substance by Polyphloretin Phosphate

Abstract

Polyphloretin phosphate (PPP), a compound with prostaglandin and enzyme inhibitory activities, inhibited the release of histamine from rat mast cells induced by compound 48/80 or bee venom but had no effect on the release of histamine produced by chlorpromazine or n‐decylamine. In perfused cat paws (compound 48/80) and in guinea pig lung tissue (antigen) the histamine release and the formation of slow reacting substance were both inhibited by PPP. The blood pressure lowering effect of compound 48/80 in the cat was antagonized by the intravenous administration of PPP. Experiments with fractionated (dialysed) PPP showed that the high molecular weight fractions of PPP were more potent that the low molecular weight fractions in inhibiting histamine release from rat mast cells. Polyphloroglucinol phosphate, a polymer of the same type as PPP but devoid of any prostaglandin inhibitory (IPG) activity, inhibited the release processes in a manner similar to PPP, indicating that the IPG‐activity of PPP is not associated with its capacity to inhibit release. It is suggested that the inhibition by PPP of the release processes studied may be due, at least partly, to a chemical interaction between inhibitor and releasing agent.