EXTRACELLULAR GUANOSINE 3',5'-CYCLIC-MONOPHOSPHATE AND DISODIUM-CROMOGLYCATE SHARE A SIMILAR SPECTRUM OF ACTIVITY IN THE INHIBITION OF HISTAMINE-RELEASE FROM ISOLATED MAST-CELLS AND BASOPHILS

In comparison to adenosine 3',5'-cyclic monophosphate (cAMP), surprisi ngly little is known regarding the role of guanosine 3',5'-cyclic mono phosphate (cGMP) in the functional modulation of mast cells and basoph ils. In the present study, the ability of cGMP, cAMP, and a range of r elated compounds, to inhibit immunologically induced histamine release from these cells was investigated and compared to the anti-asthmatic drug disodium cromoglycate (DSCG). Exogenously applied cGMP produced a potent inhibition of histamine release from rat peritoneal mast cells , but cAMP had a negligible effect. The attenuation noted with cGMP wa s markedly reduced if cells were pretreated with the nucleotide before stimulation. Similar results were obtained with DSCG. The inhibitory and tachyphylactic effects noted with cGMP were mimicked by direct der ivatives of the compound but not by a range of other cyclic or guanosi ne nucleotides. The time courses of the induced tachyphylaxis seen wit h cGMP and DSCG were similar, and cross-tachyphylaxis between the two compounds was observed. In addition, both cGMP and DSCG showed a compa rable spectrum of activity against mast cells isolated from the mouse, guinea pig, and human. The parallel effects of the two agents suggest s that they inhibit mediator release from mast cells through similar m echanisms.