BACKGROUND: Although @entity1672 (PGD2), a mast cell-derived inflammatory mediator, may trigger @entity32 , its potency and the mechanism by which it induces airway microvascular leakage, a component of airway @entity32 , is not clear. OBJECTIVE: We wanted to evaluate the relative potency of PGD2 to cause microvascular leakage as compared to airflow obstruction, because both responses were shown to occur simultaneously in allergic @entity1030 such as @entity565 . The role of @entity2871 A2 receptors (TP receptors) in inducing these airway responses was also examined. METHODS: Anesthetized and mechanically ventilated @entity840 were given i.v. @entity5934 ( @entity5934 ) and, 1 min later, PGD2 (30, 100, 300 or 1,000 nmol/kg). For comparison, the effect of 150 nmol/kg @entity112 or 2 nmol/kg @entity15491 (LTD4) was also examined. Lung resistance (R(L)) was measured for 6 min (or 25 min for selected animals) and the lungs were removed to calculate the amount of extravasated @entity5934 into the airways as a marker of leakage. In some of the animals, specific TP receptor antagonists, @entity20156 (10 microg/kg) or @entity17757 (10 mg/kg), or a @entity2871 A2 synthase inhibitor, @entity17756 (30 mg/kg), was pretreated before giving PGD2. RESULTS: Injection of PGD2 produced an immediate and dose-dependent increase in RL (peaking within 1 min), which was significant at all doses studied. At 1,000 nmol/kg, PGD2 induced a later increase in R(L), starting at 3 min and reaching a second peak at 8 min. By contrast, only PGD2 at doses of 300 and 1,000 nmol/kg produced a significant increase in @entity5934 extravasation. The relative potency of 1,000 nmol/kg PGD2 to induce leakage as compared to airflow obstruction was comparable to @entity112 at most of airway levels, but less than LTD4. Both responses caused by PGD2 were completely abolished by @entity20156 and @entity17757 , but not by @entity17756 . CONCLUSION: PGD2 may induce airway microvascular leakage by directly stimulating TP receptors without generating TXA2 in @entity840 . @entity2680 may play a role in the development of @entity32 caused by PGD2.

Acute effects of XXXX to induce airflow obstruction and airway microvascular leakage in @entity840 : role of @entity2871 A2 receptors.

@entity2871 :: ('CHEBI:26995', 'Chemical') :: ['thromboxane'] @entity32 :: ('MESH:D007249', 'Disease') :: ['allergic airway inflammation', 'inflammation'] @entity1672 :: ('MESH:D015230', 'Chemical') :: ['prostaglandin D2'] @entity2680 :: ('MESH:D003763', 'Disease') :: ['Microvascular leakage'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity840 :: ('10141', 'Species') :: ['guinea pigs'] @entity112 :: ('MESH:D006632', 'Chemical') :: ['histamine'] @entity15491 :: ('MESH:D017998', 'Chemical') :: ['leukotriene D4'] @entity5934 :: ('MESH:C536380', 'Disease') :: ['Evans blue dye', 'EB dye'] @entity1030 :: ('MESH:D029424', 'Disease') :: ['airway diseases'] @entity20156 :: ('MESH:C056566', 'Chemical') :: ['S-1452'] @entity17756 :: ('MESH:C034364', 'Chemical') :: ['OKY-046'] @entity17757 :: ('MESH:C049855', 'Chemical') :: ['ONO-3708']
@entity1672 :: (MESH:D015230,Chemical) :: ['prostaglandin D2']
