Watanabe T, Duncan R, Lockey R F, Krzanowski J J
Department of Pharmacology and Therapeutics, College of Medicine, University of South Florida, Tampa.
Arch Int Pharmacodyn Ther. 1988 Sep-Oct;295:204-10.
The phenomenon of histamine tachyphylaxis in vitro previously observed in the airway smooth muscle from adult dogs was investigated in airway smooth muscle from young dogs (age 72-96 days; mean: 91 days). Tachyphylaxis was demonstrated by repetitive exposure to 10(-4) M histamine (4th contractile response was 53.0 +/- 4.9% of the initial histamine contraction; n = 6, P less than 0.01). This result was similar to that previously reported (Anderson et al., 1979) in adult canine tracheal smooth muscle. Tachyphylaxis to histamine was demonstrated also by repetitive exposure to histamine (10(-4) M) in the small airway smooth muscle (2 mm diameter), (4th contractile response was 59.6 +/- 7.2% of the initial histamine contraction; n = 6, P less than 0.01). This tachyphylaxic response is not present in the small airways from adult animals. The development of histamine tachyphylaxis in both tracheal and small airway smooth muscle could be prevented or reversed by preincubation of the tissue with indomethacin (2.8 x 10(-6) M). The composite information thus implicates prostaglandins as the most probable mediators of the process. These results suggest that the variable phenomenon of histamine tachyphylaxis is dependent on the maturity of the animal and on the size of the airway.
在幼龄犬(72 - 96日龄;平均:91日龄)的气道平滑肌中,研究了先前在成年犬气道平滑肌中观察到的组胺快速耐受性现象。通过重复暴露于10⁻⁴M组胺来证明快速耐受性(第4次收缩反应为初始组胺收缩的53.0±4.9%;n = 6,P < 0.01)。该结果与先前在成年犬气管平滑肌中报道的结果(Anderson等人,1979年)相似。在小气道平滑肌(直径2mm)中重复暴露于组胺(10⁻⁴M)也证明了对组胺的快速耐受性(第4次收缩反应为初始组胺收缩的59.6±7.2%;n = 6,P < 0.01)。成年动物的小气道中不存在这种快速耐受性反应。通过用吲哚美辛(2.8×10⁻⁶M)预孵育组织,可以预防或逆转气管和小气道平滑肌中组胺快速耐受性的发展。因此,综合信息表明前列腺素是该过程最可能的介质。这些结果表明,组胺快速耐受性的可变现象取决于动物的成熟度和气道的大小。