Yamasaki M, Mizutani N, Sasaki K, Nabe T, Matsumoto T, Ashida Y, Kohno S
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan.
Inflamm Res. 2001 Sep;50(9):466-73. doi: 10.1007/PL00000272.
We investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness to histamine using a guinea pig model of allergic rhinitis.
Male Hartley guinea pigs were used.
Intranasally sensitized guinea pigs were challenged once every week for 13 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 4th, 6th and 13th challenge.
Sneezing frequency and the change in specific airway resistance (sRaw) were measured at these challenges. Two days after the 13th challenge, nasal responsiveness to histamine was evaluated by measuring sRaw after intranasal instillation of increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th challenge.
Only terfenadine (10 mg/kg) significantly inhibited sneezing at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late phase elevation of sRaw (biphasic nasal blockage), although the degree of inhibition on the early phase response varied with the challenge time. In contrast, the development of nasal hyperresponsiveness to histamine was inhibited by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and histamine in NCLF were observed after the challenge in sensitized animals.
These results suggest that TXA2 and p-LTs, but not histamine, play important roles in both the early and the late phase nasal blockage in this model of allergic rhinitis.
我们使用变应性鼻炎豚鼠模型，研究了血栓素（TX）A2拮抗剂司来吉兰、肽白三烯（p-LT）拮抗剂普仑司特、抗组胺药特非那定和糖皮质激素地塞米松对抗原诱导的喷嚏、双相性鼻阻塞及鼻对组胺的高反应性的影响。
使用雄性Hartley豚鼠。
经鼻致敏的豚鼠每周吸入日本柳杉花粉作为抗原进行激发，共13周。在第4、6和13次激发前3小时和1小时分别口服地塞米松和其他药物。
在这些激发时测量喷嚏频率和比气道阻力（sRaw）的变化。第13次激发后两天，通过鼻内滴入递增剂量组胺后测量sRaw来评估鼻对组胺的反应性。此外，在第13次激发时收集的鼻腔灌洗液（NCLF）中估计TXB2、p-LTs和组胺的水平。
仅特非那定（10mg/kg）在任何激发时间均能显著抑制喷嚏。司来吉兰（3和10mg/kg）、普仑司特（30mg/kg）和地塞米松（10mg/kg）可抑制sRaw的早期和晚期升高（双相性鼻阻塞），但特非那定不能，尽管对早期反应的抑制程度随激发时间而异。相反，仅地塞米松可抑制鼻对组胺高反应性的发展。此外，致敏动物激发后NCLF中TXB2、p-LTs和组胺呈双相增加。
这些结果表明，在该变应性鼻炎模型中，TX A2和p-LTs而非组胺在早期和晚期鼻阻塞中起重要作用。
