Yousufzai S Y, Zheng P, Abdel-Latif A A
Department of Biochemistry and Molecular Biology, Medical College of Augusta 30912.
Exp Eye Res. 1994 May;58(5):513-22. doi: 10.1006/exer.1994.1045.
In the present study it is demonstrated that in bovine ciliary muscle, muscarinic stimulation results in: (a) release of 14C-arachidonic acid (14C-AA) and 14C-labeled prostaglandins (PGs) from muscle prelabeled with 14C-AA; (b) release of endogenous PGs, measured by means of radioimmunoassay; (c) enhanced IP3 production and (d) muscle contraction. In addition, PGs, such as PGE2 and PGD2, increased cAMP formation and induced muscle relaxation. The studies on the kinetics of 14C-AA metabolism revealed that incorporation of 14C-AA into glycerolipids and its conversion into PGs by the ciliary muscle were rapid and time-dependent. The amounts of 14C-radioactivity recovered in the major PGs decreased in the following order: PGD2 > PGE2 < PGF2 alpha > 6-keto-PGF1 alpha. The rate of endogenous PGF2 alpha synthesis by iris-ciliary body tissues from different mammalian species was found to be in the following order: ciliary muscle < ciliary processes < sphincter muscle. The EC50s for muscarinic-stimulated release of 14C-AA, 14C-labeled PGs, and endogenous PGF2 alpha and PGE2, and for IP3 production and contraction of the ciliary muscle indicate that CCh is 2-16 times as potent as pilocarpine in eliciting these responses, with the greatest difference being for contraction. The maximal increase in ciliary muscle tension due to CCh was 48% greater than that evoked by pilocarpine. All PGs tested, including PGE2, 17-phenyl trinor PGE2, 11-deoxy PGE1, PGF2 alpha and PGD2 had no effect on IP3 production and contraction in the ciliary muscle. However, PGE2 and PGD2 stimulated cAMP formation and inhibited CCh-induced IP3 production in a dose-dependent manner. In addition, PGE2 and PGD2 induced relaxation in ciliary muscle precontracted by CCh. In presence of indomethacin (1 microM), the CCh-induced contraction was greater than that observed in absence of the cyclo-oxygenase inhibitor. It is suggested that in the ciliary muscle certain PGs, such as PGE2 and PGD2, may function to modulate, via cAMP, the responses to muscarinic stimulation in this tissue.
在本研究中已证明，在牛睫状肌中，毒蕈碱刺激会导致：(a) 从预先用14C-花生四烯酸（14C-AA）标记的肌肉中释放14C-花生四烯酸（14C-AA）和14C标记的前列腺素（PGs）；(b) 通过放射免疫测定法测量内源性PGs的释放；(c) 肌醇三磷酸（IP3）生成增加；以及(d) 肌肉收缩。此外，PGs，如前列腺素E2（PGE2）和前列腺素D2（PGD2），会增加环磷酸腺苷（cAMP）的形成并诱导肌肉松弛。对14C-AA代谢动力学的研究表明，睫状肌将14C-AA掺入甘油脂质并将其转化为PGs的过程迅速且具有时间依赖性。在主要PGs中回收的14C放射性活度按以下顺序降低：PGD2 > PGE2 < 前列腺素F2α（PGF2α）> 6-酮-前列腺素F1α（6-keto-PGF1α）。发现来自不同哺乳动物物种的虹膜-睫状体组织合成内源性PGF2α的速率按以下顺序排列：睫状肌 < 睫状突 < 括约肌。毒蕈碱刺激释放14C-AA、14C标记的PGs以及内源性PGF2α和PGE2，以及IP3生成和睫状肌收缩的半数有效浓度（EC50）表明，在引发这些反应方面，氯化乙酰胆碱（CCh）的效力是毛果芸香碱（pilocarpine）的2至16倍，其中收缩方面的差异最大。CCh引起的睫状肌张力最大增加比毛果芸香碱引起的高48%。所有测试的PGs，包括PGE2、17-苯基三降PGE2、11-脱氧PGE1、PGF2α和PGD2，对睫状肌中的IP3生成和收缩均无影响。然而，PGE2和PGD2以剂量依赖性方式刺激cAMP形成并抑制CCh诱导的IP3生成。此外，PGE2和PGD2诱导由CCh预收缩的睫状肌松弛。在吲哚美辛（1 microM）存在的情况下，CCh诱导的收缩比在没有环氧化酶抑制剂时观察到的更大。有人提出，在睫状肌中，某些PGs，如PGE2和PGD2，可能通过cAMP发挥作用，调节该组织对毒蕈碱刺激的反应。
