Evidence against a role of cyclic nucleotides in the regulation of anaphylactic histamine release in isolated rat mast cells

Abstract

The effect of different phosphodiesterase (PDE) inhibitors on the antigen or 48/80 induced histamine release from isolated hooded Lister rat mast cells was tested. The unselective PDE inhibitors theophylline (2.5 mM) and IBMX (0.2 mM) and the selective cGMP PDE inhibitor M and B 22948 (0.1 mM) inhibited the antigen induced histamine release by 50% while 48/80 induced release was inhibited by about 25%. The cAMP selective PDE inhibitors ICI 63197 (0.5 mM) or Ro 20-1724 (0.2 mM) had no effect on 48/80 induced histamine release but tended to enhance antigen induced release. There was no correlation between the measured levels of cAMP and the effect on histamine release by the investigated PDE inhibitors. cAMP or cGMP up to 10-3 M did not affect the anaphylactic histamine release. Dibutyryl-cAMP and dibutyryl-cGMP (10-4 M) both inhibited the release about 20% but this effect could be explained by the effect of butyric acid as sodium butyrate (2 .times. 10-4 M) also inhibited the release by 20%. Cyclic nucleotides are evidently not important regulators of histamine release from isolated mast cells.