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), surprisingly little is known regarding the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the functional modulation of mast cells and basophils. In the present study, the ability of cGMP, cAMP, and a range of related 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 was 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 derivatives of the compound but not by a range of other cyclic or guanosine nucleotides. The time courses of the induced tachyphylaxis seen with cGMP and DSCG were similar, and cross-tachyphylaxis between the two compounds was observed. In addition, both cGMP and DSCG showed a comparable spectrum of activity against mast cells isolated from the mouse, guinea pig, and human. The parallel effects of the two agents suggests that they may inhibit mediator release from mast cells through similar mechanisms.
Mackay
G A
GA
Department of Chemistry, University College London, UK.
Pearce
F L
FL
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology; D001491:Basophils / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000276:immunology; D002469:Cell Separation; D004205:Cromolyn Sodium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology*; D005110:Extracellular Space / Q000276:immunology*; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013618:Tachyphylaxis / Q000276:immunology
D006633:Histamine Antagonists; D009599:Nitroprusside; D000242:Cyclic AMP; D006152:Cyclic GMP; D004205:Cromolyn Sodium