The inhibition of histamine release from guinea-pig lung by compound I.C.I. 74917 and isoprenaline.

Abstract

Compounds that increase tissue concentrations of cyclic AMP inhibit the release of histamine from sensitized tissues when they are challenged with antigen. It has been proposed that the anti-asthmatic agent disodium cromoglycate exerts its anti-allergic properties by inhibiting cyclic AMP phosphodiesterase. This hypothesis was based on experiments where it was shown that the inhibition of antigen-induced mast-cell degranulation by isoprenaline and disodium cromoglycate was synergistic (Taylor et al., 1974), and experiments that showed that disodium cromoglycate was a phosphodiesterase inhibitor (Ray & Warren, 1974). Compound I.C.I. 74917, Bufrolin (6-n-butyl-2,8-dicarboxy-4,10-dioxo-1,4,7,10tetrahydro-l,7-phenanthroline) is a potent inhibitor of immediate hypersensitivity reactions in guinea-pig lung and rat mast cells (Evans & Thomson, 1975). It demonstrates inhibition characteristics in lung similar to those of disodium cromoglycate in mast cells, including the critical time of addition relative to antigen (see Fig. la) and the development of tolerance (K. J. Barrett-Bee, unpublished work). However, it is active at onehundredth the dose that disodium cromoglycate is active in vitro. The work described below investigated the allergic release of histamine from guineapig lung and its inhibition by compound I.C.I. 74917 and isoprenaline, alone and in combination, to assess the nature of the inhibition.