EFFECT OF H-1-ANTIHISTAMINES ON HISTAMINE-RELEASE FROM DISPERSED CANINE CUTANEOUS MAST-CELLS

Objective-Because of the implication of histamine in canine atopic der matitis, H-1-antihistamines may provide a valid alternative to glucoco rticoid therapy. In vitro study of these drugs prior to clinical testi ng can allow the most promising compounds to be selected for trials an d render trials with drugs of doubtful efficacy unnecessary. Sample Po pulation-Isolated canine cutaneous mast cells. Procedure-Cells were pr eincubated with antihistamines at increasing concentrations and incuba ted with concanavalin A (1,000 mu g/ml), calcium ionophore A23187 (1 m u M), and substance P (100 mu m). Compound 48/80 was not used because it proved to be cytotoxic. Results-Generally, significant prodegranula ting effect was not observed for most of the studied agents. Only terf enadine increased spontaneous histamine release at concentrations > 30 mu M. Cetirizine did not block histamine release at any of the studie d concentrations. Ketotifen had a low inhibitory effect only at the hi ghest concentration (100 mu M) after concanavalin A- (23.6 +/- 2.8%) a nd calcium ionophore A23187 (29.8 +/- 3.0%) induced release. Terfenadi ne caused a concentration-dependent inhibitory effect after ionophore A23187- (48.1 +/- 2.2%) and concanavalin A- (28.9 +/- 2.3%) activation , but was inactive against substance P-induced release. In contrast, l oratadine had potent dose-dependent inhibition of concanavalin A- and ionophore A23187-induced histamine release, with maximal effect of 85. 6 +/- 3.1% and 62.6 +/- 4.7%, respectively, at 100 mu M concentration. After substance P activation, histamine release was only slightly inh ibited by loratadine (14.8 +/- 1.1%). Conclusions-This study documents the behavior of isolated canine cutaneous mast cells in the presence of nonimmunologic stimulation. Using this in vitro method, we were abl e to determine that loratadine is the only antihistamine that has pote nt inhibition of histamine release from dog cutaneous mast cells witho ut a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing.