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前列腺素D2的眼部药理学研究。

Studies on the ocular pharmacology of prostaglandin D2.

作者信息

Woodward D F, Hawley S B, Williams L S, Ralston T R, Protzman C E, Spada C S, Nieves A L

机构信息

Allergan, Inc., Department of Pharmacology, Irvine, California 92715.

出版信息

Invest Ophthalmol Vis Sci. 1990 Jan;31(1):138-46.

PMID:2298534
Abstract

Prostaglandin D2 (PGD2) exerts a variety of biologic actions in the eye; these include ocular hypotension and inflammatory effects on the conjunctiva. The profile of activity of PGD2 in ocular tissues was compared to that of BW 245C, a selective agonist for the PGD2-sensitive (DP) receptor, and to that of the biologically active metabolites of PGD2, 9 alpha,11 beta-prostaglandin F2 (9 alpha,11 beta-PGF2) and prostaglandin J2 (PGJ2). PGD2 produced a dose-dependent decrease in intraocular pressure and in the conjunctiva it caused increased conjunctival microvascular permeability, eosinophil infiltration and goblet cell depletion. Although BW 245C was equipotent to PGD2 as an ocular hypotensive agent, it did not cause pathological effects in the conjunctiva. Thus, the ocular hypotensive effect of PGD2 may be separated from inflammatory effects on the conjunctiva by employing a selective DP-receptor agonist such as BW 245C. 9 alpha,11 beta-PGF2 was a weak ocular hypotensive and did not cause conjunctival inflammation. PGJ2 produced no significant effect on intraocular pressure. PGJ2 did not elicit a microvascular permeability response in the conjunctiva, but was inflammatory in other respects and caused eosinophil infiltration and goblet cell depletion similar to PGD2. Thus, both the ocular hypotensive actions and the conjunctival pathology of PGD2 may be replicated individually by employing PGD2 analogues and metabolites.

摘要

前列腺素D2(PGD2)在眼部发挥多种生物学作用;这些作用包括降低眼压以及对结膜产生炎症效应。将PGD2在眼组织中的活性概况与BW 245C(一种对PGD2敏感的(DP)受体的选择性激动剂)以及PGD2的生物活性代谢产物9α,11β-前列腺素F2(9α,11β-PGF2)和前列腺素J2(PGJ2)的活性概况进行了比较。PGD2可使眼压呈剂量依赖性降低,在结膜中,它会导致结膜微血管通透性增加、嗜酸性粒细胞浸润和杯状细胞减少。尽管BW 245C作为一种降眼压药物与PGD2等效,但它不会在结膜中引起病理效应。因此,通过使用选择性DP受体激动剂如BW 245C,可将PGD2的降眼压作用与对结膜的炎症作用区分开来。9α,11β-PGF2是一种较弱的降眼压药物,且不会引起结膜炎症。PGJ2对眼压没有显著影响。PGJ2不会在结膜中引发微血管通透性反应,但在其他方面具有炎症性,会导致嗜酸性粒细胞浸润和杯状细胞减少,与PGD2类似。因此,通过使用PGD2类似物和代谢产物,可以分别重现PGD2的降眼压作用和结膜病理变化。

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