INHIBITION OF HISTAMINE-RELEASE FROM DISPERSED CANINE SKIN MAST-CELLSBY CYCLOSPORINE-A, ROLIPRAM AND SALBUTAMOL, BUT NOT BY DEXAMETHASONE OR SODIUM CROMOGLYCATE

Despite the important role that canine skin mast cells play in IgE-med iated allergic inflammation, clinically useful compounds for modulatin g mediator release from these cells or for suppressing cell response a re lacking in the dog. The ability of five compounds to inhibit histam ine release induced by non immunological (calcium ionophore A23187 and substance P) and IgE-dependent (concanavalin A) stimuli were compared . Sodium cromoglycate, a mast cell stabilizer, and dexamethasone, a gl ucocorticoid, failed to inhibit histamine release from isolated skin m ast cells following any kind of stimulation. Salbutamol, a beta-adrene rgic agonist, exhibited inhibitory activity (46.0%) only after concana valin A activation. In contrast, rolipram, a selective phosphodiestera se IV inhibitor and cyclosporin A, an immunosuppressor, showed potent anti allergic actions, inhibiting both IgE-dependent and -independent stimuli. Rolipram inhibited 42.8%, 44.7% and 19.2% of the mediator rel ease induced by ionophore A23187, substance P and concanavalin A, resp ectively. Similarly cyclosporin A induced 85.9%, 14.9% and 67.3% inhib ition after ionophore A23187, substance P and concanavalin A stimulati on, respectively. These results suggest that rolipram and cyclosporin A merit to be clinically tested as agents for the treatment of chronic allergic diseases in the dog.