Effect of H1-antihistamines on histamine release from dispersed canine cutaneous mast cells.
OBJECTIVE
Because of the implication of histamine in canine atopic dermatitis, H1-antihistamines may provide a valid alternative to glucocorticoid therapy. In vitro study of these drugs prior to clinical testing can allow the most promising compounds to be selected for trials and render trials with drugs of doubtful efficacy unnecessary.


METHODS
Isolated canine cutaneous mast cells.


METHODS
Cells were preincubated with antihistamines at increasing concentrations and incubated with concanavalin A (1,000 micrograms/ml), calcium ionophore A23187 (1 microM), and substance P (100 microM). Compound 48/80 was not used because it proved to be cytotoxic.


RESULTS
Generally, significant prodegranulating effect was not observed for most of the studied agents. Only terfenadine increased spontaneous histamine release at concentrations > 30 microM. Cetirizine did not block histamine release at any of the studied concentrations. Ketotifen had a low inhibitory effect only at the highest concentration (100 microM) after concanavalin A- (23.6 +/- 2.8%) and calcium ionophore A23187- (29.8 +/- 3.0%) induced release. Terfenadine 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, loratadine 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 microM concentration. After substance P activation, histamine release was only slightly inhibited 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 able to determine that loratadine is the only antihistamine that has potent inhibition of histamine release from dog cutaneous mast cells without a substantial prodegranulating effect. Loratadine is, therefore, a good candidate for clinical testing.
García
G
G
Department de Farmacología i Terapèutica, Universitat Autònoma de Barcelona, Bellaterra, Spain.
DeMora
F
F
Ferrer
L
L
Puigdemont
A
A
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D017332:Cetirizine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000662:veterinary; D004283:Dog Diseases; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D017336:Loratadine / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D013373:Substance P / Q000494:pharmacology; D016593:Terfenadine / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D003208:Concanavalin A; D013373:Substance P; D000001:Calcimycin; D017336:Loratadine; D016593:Terfenadine; D007665:Ketotifen; D017332:Cetirizine