United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Int Arch Allergy Immunol. 2012;158(4):359-68. doi: 10.1159/000334555. Epub 2012 Apr 3.
Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D(2) (PGD(2)), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear.
The effect of PGD(2) on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD(2), and to examine the mechanism of PGD(2)-induced nasal congestion. Moreover, the involvement of second messengers in PGD(2)-induced mucosal relaxation was investigated.
PGD(2) induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue.
PGD(2)-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD(2)-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.
变应性鼻炎是最常见的过敏性疾病，表现为典型的鼻塞症状。前列腺素 D₂（PGD₂），一种在人类过敏刺激时由肥大细胞大量释放的化学介质，已知与鼻塞有关。然而，这种鼻塞发生的机制尚不清楚。
使用一种非侵入性的方法测量 PGD₂对豚鼠鼻腔气流的影响，该方法避免了任何麻醉作用。采用等长张力法测定分离的鼻黏膜和鼻血管腐蚀树脂铸型技术，以阐明受 PGD₂影响的鼻黏膜血管面积，并研究 PGD₂引起的鼻塞机制。此外，还研究了第二信使在 PGD₂诱导的黏膜松弛中的作用。
PGD₂在变应性鼻炎豚鼠模型中引起鼻腔内压增加。此外，使用血管腐蚀树脂铸型技术，在鼻黏膜中发现鼻中隔周围的窦状微血管扩张。此外，刺激前列腺素 DP-1 受体后，鼻黏膜松弛与组织中环腺苷酸（cAMP）水平相关。
PGD₂引起的鼻塞是通过增加鼻黏膜中环腺苷酸（cAMP）水平直接扩张窦状血管引起的，表明 PGD₂引起的鼻塞机制与其他化学介质不同。因此，前列腺素 DP-1 受体拮抗剂可能是缓解鼻塞的一种替代方法。或者，联合使用其他参与鼻塞的介质拮抗剂也可能是治疗变应性鼻炎的一种有价值的治疗方法。
