Johnston S L, Smith S, Harrison J, Ritter W, Howarth P H
Immunopharmacology Group, Southampton General Hospital, UK.
J Allergy Clin Immunol. 1993 Apr;91(4):903-9. doi: 10.1016/0091-6749(93)90348-j.
Nasal lavage and challenge studies in allergic rhinitis implicate prostaglandin (PG) D2 in the genesis of nasal blockage. PG D2 is known to act via at least two receptors, the thromboxane prostanoid receptor and the PG D2 prostanoid (DP) receptor; the lower airway effects are mediated chiefly by the TP receptor. The receptor involved in the genesis of PG D2-induced nasal blockage is unknown. BAY u 3405 is a potent selective competitive TP receptor antagonist, which inhibits the lower airway response to PG D2, and shifts the dose-response curve to the right by up to 16-fold.
The efficacy of a single oral dose of 20 mg of BAY u 3405 was examined in comparison with PG D2 nasal insufflation in a randomized, double-blind, placebo-controlled crossover study, with objective measurement of nasal resistance by active posterior rhinomanometry.
BAY u 3405 afforded no protection against PG D2-induced nasal blockage.
This suggests that PG D2-induced nasal blockage may be mediated by the DP receptor rather than the TP receptor and that TP receptor antagonists are unlikely to be of benefit in the treatment of allergic rhinitis. In vivo investigation with specific potent DP receptor antagonists is awaited.
变应性鼻炎的鼻腔灌洗和激发试验表明，前列腺素（PG）D2与鼻阻塞的发生有关。已知PG D2至少通过两种受体发挥作用，即血栓素前列腺素受体和PG D2前列腺素（DP）受体；下呼吸道效应主要由TP受体介导。PG D2诱导鼻阻塞发生所涉及的受体尚不清楚。BAY u 3405是一种强效选择性竞争性TP受体拮抗剂，可抑制下呼吸道对PG D2的反应，并使剂量反应曲线右移高达16倍。
在一项随机、双盲、安慰剂对照的交叉研究中，通过主动后鼻测压法客观测量鼻阻力，比较单次口服20 mg BAY u 3405与PG D2鼻腔内注入的疗效。
BAY u 3405对PG D2诱导的鼻阻塞无保护作用。
这表明PG D2诱导的鼻阻塞可能由DP受体而非TP受体介导，且TP受体拮抗剂不太可能对变应性鼻炎的治疗有益。有待使用特异性强效DP受体拮抗剂进行体内研究。
