Inhibition of antigen-induced histamine release from rat mast cells by a cyclic GMP-phosphodiesterase inhibitor and sodium nitrite

Abstract

Antianaphylactic properties have been attributed to cyclic nucleotide phosphodiesterase inhibitors through increase of cyclic AMP levels, according to the concept that increases in cyclic AMP reduce release and increases in cyclic GMP enhance release. However, Coulson et al. [3] showed that the inhibition of histamine release from human lung is correlated to the inhibition of cyclic GMP hydrolysis. We studied the effect of specific inhibitors of cyclic AMP and cyclic GMP hydrolysis on the antigen-induced mediator release from rat mass cells and human basophils and on airways relaxation [4]. The results suggested that the modulation of mediator release was different from one cell type to the other, enhancement of cyclic AMP levels leading to the inhibition of release from basophils, while cyclic GMP appears to be predominantly involved in mast cells. The present paper shows that high concentrations of sodium nitrite, a stimulating agent of guanylate cyclase, inhibit histamine release from rat mast cells in the presence or absence of M&B 22948, a selective cyclic GMP phosphodiesterase inhibitor.