Abstract
Several possible mechanisms capable of inducing the anti-bronchoconstrictor effects of eprozinol have been investigated in vitro by means of the following techniques: (l)test for inhibition of mast cell histamine release, secondary to a passive anaphylactic response on human lung tissue; (2) determination of the type of interference with the contracting effects of bradykinin, acetylcholine and serotonin; (3) interference with the smooth muscle contraction induced by BaCl2 or CaCl2; (4) investigation of blockade by propranolol of eprozinol-induced relaxation of tracheal muscle; (5) investigation of changes in cAMP and cGMP levels in guinea pig trachea; (6) investigation of an inhibitory effect on phosphodiesterase. When the immunological reaction is carried out while eprozinol is in contact with the lung preparation, the compound appears more effective than disodium cromoglycate but less effective than isoprenaline in inhibiting mast cell degranulation. In fact, a 40% inhibition of mast cell histamine release occurs with a concentration of eprozinol at 2 x 10–6M. On the other hand, when the preparations are rinsed between the period of incubation with the compound and the addition of antigen, only disodium cromoglycate still manifests significant inhibitory activity. Eprozinol antagonises serotonin, bradykinin and acetylcholine in a non-competitive fashion (pD2 = 4.21 ± 0.09; 3.81 ± 0.07 and 4.17 ± 0.07, respectively). Eprozinol non-specifically antagonises BaCl2 (ileum or tracheal muscle from the guinea pig) and CaCl2 (KC1-depolarised guinea pig caecum). The relaxant effects on calf tracheal smooth muscle are characterised by the following parameters: isoprenaline, pD2 = 7.93 ± 0.21 and eprozinol, pD2 = 4.37 ± 0.17. With guinea pig trachea, these parameters are: isoprenaline, pD2 = 6.7 ± 0.10 and eprozinol, pD2 = 2.5 ± 0.09. In all cases the intrinsic activity of both compounds is the same (α = 1). No significant changes in cAMP and cGMP levels are observed in guinea pig trachea, with eprozinol or isoprenaline, at doses capable of inducing relaxation. Eprozinol is only a very weak phosphodiesterase inhibitor, at large concentrations.