Yousufzai S Y, Abdel-Latif A A
Invest Ophthalmol Vis Sci. 1987 Mar;28(3):409-19.
Topical treatment of the rabbit eye with three successive doses of 2% epinephrine resulted in attenuation of the in vitro drug response of the alpha 1-adrenoceptor-mediated phosphoinositide hydrolysis system and of alpha 1-adrenergic receptor-mediated contraction in the iris. In contrast, sympathetic denervation of the eye resulted in potentiation of these responses. Desensitized tissues showed a significant decrease in epinephrine-induced myo-inositol trisphosphate (IP3) accumulation, 1,2-diacylglycerol (DG) formation, measured as phosphatidate, arachidonic acid (AA) liberation, measured by radiochromatography, prostaglandin (PG) E2 release, measured by radiochromatography and radioimmunoassay, and muscle contraction. Adrenergic desensitization of the eye resulted in attenuation of: The polyphosphoinositide response in the iris, measured both as loss of 32P-radioactivity from phosphatidylinositol 4,5-bisphosphate (PIP2) and as IP3 accumulation; the epinephrine-stimulated liberation of AA, from membrane phosphoinositides and other phospholipids, and PGE2 release in the iris; and the epinephrine-induced muscle contraction in the iris dilator. This adrenergic desensitization of the eye is reversible. Surgical sympathetic denervation, previously found to increase alpha 1-adrenoceptor mediated accumulation of IP3 and contraction, increased AA liberation. Dexamethasone blocked the epinephrine-induced liberation of AA and PG release, both in vivo and in vitro. These data support the hypothesis that changes in the activity of the alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis system and its derived second messengers may underlie the mechanism of adrenergic subsensitivity and supersensitivity in the iris-ciliary body. How much the desensitization of alpha 1-adrenergic receptor-mediated responses contribute to the therapeutic action of epinephrine in the eye remains to be determined.
用连续三剂2%肾上腺素对兔眼进行局部治疗，导致α1 -肾上腺素能受体介导的磷酸肌醇水解系统的体外药物反应以及虹膜中α1 -肾上腺素能受体介导的收缩减弱。相反，眼部交感神经去支配导致这些反应增强。脱敏组织中，肾上腺素诱导的肌醇三磷酸（IP3）积累、以磷脂酸衡量的1,2 -二酰基甘油（DG）形成、通过放射性色谱法测量的花生四烯酸（AA）释放、通过放射性色谱法和放射免疫测定法测量的前列腺素（PG）E2释放以及肌肉收缩均显著降低。眼部肾上腺素能脱敏导致以下情况减弱：虹膜中的多磷酸肌醇反应，以磷脂酰肌醇4,5 -二磷酸（PIP2）中32P放射性的损失和IP3积累来衡量；肾上腺素刺激的虹膜中膜磷酸肌醇和其他磷脂释放AA以及PGE2释放；以及肾上腺素诱导的虹膜开大肌收缩。眼部这种肾上腺素能脱敏是可逆的。先前发现手术性交感神经去支配可增加α1 -肾上腺素能受体介导的IP3积累和收缩，同时增加AA释放。地塞米松在体内和体外均阻断了肾上腺素诱导的AA释放和PG释放。这些数据支持以下假设：α1 -肾上腺素能受体介导的磷酸肌醇水解系统及其衍生的第二信使活性的变化可能是虹膜 - 睫状体中肾上腺素能低敏和高敏机制的基础。α1 -肾上腺素能受体介导反应的脱敏对肾上腺素在眼部治疗作用的贡献程度仍有待确定。
