Effect of H1-antihistamines on histamine release from dispersed canine cutaneous mast cells.
Effect of H1-antihistamines on histamine release from dispersed canine cutaneous mast cells.
复制标题
H1-抗组胺药对分散的犬皮肤肥大细胞释放组胺的影响。
DOI：
10.2460/ajvr.1997.58.03.293
复制
发表时间：
1997
影响因子：
1
通讯作者：
A. Puigdemont
中科院分区：
文献类型：
--
作者：
Gloria García;Fernando DeMora;Lluís Ferrer;A. Puigdemont
目的
由于组胺在犬特应性皮炎中的作用，H1-抗组胺药可能为糖皮质激素治疗提供有效的替代方案。在临床试验之前对这些药物进行体外研究，可以选择最有希望的化合物进行试验，并使疗效可疑的药物试验变得不必要。
样本群体
分离的犬皮肤肥大细胞。
程序
将细胞与浓度递增的抗组胺剂预孵育，并与伴刀豆球蛋白A（1，000微克/ml）、钙离子载体A23187（1 μ M）和P物质（100 μ M）孵育。未使用化合物48/80，因为其被证明具有细胞毒性。
结果
一般而言，大多数研究药物均未观察到显著的促脱粒作用。只有特非那定在浓度> 30 μ M时增加自发组胺释放。在任何研究浓度下，西替利嗪均未阻断组胺释放。酮替芬仅在伴刀豆球蛋白A-（23.6 +/- 2.8%）和钙离子载体A23187-（29.8 +/- 3.0%）诱导释放后的最高浓度（100 μ M）下具有低抑制作用。特非那定在离子载体A23187-（48.1 +/- 2.2%）和伴刀豆球蛋白A-（28.9 +/- 2.3%）激活后产生浓度依赖性抑制作用，但对P物质诱导的释放无活性。相反，氯雷他定对伴刀豆球蛋白A和离子载体A23187诱导的组胺释放具有有效的剂量依赖性抑制作用，在100 μ M浓度下，最大效应分别为85.6 +/- 3.1%和62.6 +/-4.7%。P物质激活后，氯雷他定仅轻微抑制组胺释放（14.8 +/- 1.1%）。
结论
本研究记录了犬皮肤肥大细胞在非免疫刺激下的行为。使用这种体外方法，我们能够确定氯雷他定是唯一一种对犬皮肤肥大细胞释放组胺具有强效抑制作用而无显著促粒化作用的抗组胺药。因此，氯雷他定是一个很好的临床试验候选药物。
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.
SAMPLE POPULATION
Isolated canine cutaneous mast cells.
PROCEDURE
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.