Abdel-Latif A A
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
Prog Clin Biol Res. 1989;312:53-72.
In the anterior segment of the eye, phosphoinositides of the iris-ciliary body are the major source of AA for PG biosynthesis. In the past several years, we have demonstrated that these phospholipids are highly enriched in AA and have an extremely high metabolic turnover. We have also discovered that their metabolism by phospholipase C, which leads to the formation of IP3 and DG and the liberation of AA, is controlled by the following Ca2+-mobilizing receptors: alpha 1-adrenergic, M3- or M4-muscarinic cholinergic, substance P, and PGs. The release of IP3, DG, and AA in the iris was also demonstrated under in vivo conditions. Furthermore, it was demonstrated that this release is associated with denervation supersensitivity and subsensitivity of the iris. Two pathways have been demonstrated in the iris through which AA can be released directly from phosphoinositides: (a) Phosphoinositides can be hydrolyzed by phospholipase C, followed by hydrolysis of DG via lipases to liberate AA, and (b) AA can be released directly from phosphoinositides via phospholipase A2. Although the evidence for a link between Ca2+-mobilizing receptors and phospholipase C, via G proteins, has been well established, the precise link between these receptors and phospholipase A2 is still unclear. Our studies indicated that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation. In addition, evidence of a link between the two pathways through the Ca2+ signaling system has been suggested. In the iris, PAF was found to liberate AA from phosphoinositides through the phospholipase A2, but not the phospholipase C pathway, thus emphasizing the role of this pathway in PG synthesis in the eye. These findings demonstrate that AA release and, consequently, PG synthesis in the iris of the eye are exquisitely regulated. In some species, such as bovine, cat and dog, PGs were found to act as full Ca2+ mobilizing agonists. It is possible that PGs function to maintain muscle tone in the resting iris smooth muscle cells, in addition to their involvement in various Ca2+-dependent processes. Our studies indicate that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
在眼球前段，虹膜睫状体的磷酸肌醇是花生四烯酸（AA）用于前列腺素（PG）生物合成的主要来源。在过去几年中，我们已经证明这些磷脂富含AA且具有极高的代谢周转率。我们还发现，磷脂酶C对其进行的代谢，会导致肌醇三磷酸（IP3）和二酰甘油（DG）的形成以及AA的释放，这一过程受以下钙动员受体控制：α1 - 肾上腺素能受体、M3或M4 - 毒蕈碱胆碱能受体、P物质和PG。在体内条件下也证实了虹膜中IP3、DG和AA的释放。此外，还证明了这种释放与虹膜的去神经超敏反应和低敏反应有关。在虹膜中已证实有两条途径可使AA直接从磷酸肌醇中释放出来：（a）磷酸肌醇可被磷脂酶C水解，随后DG通过脂肪酶水解以释放AA；（b）AA可通过磷脂酶A2直接从磷酸肌醇中释放出来。尽管通过G蛋白在钙动员受体和磷脂酶C之间建立联系的证据已确凿，但这些受体与磷脂酶A2之间的确切联系仍不清楚。我们的研究表明，PG可能通过增加IP3积累从而促进钙动员，并通过提高环磷酸腺苷（cAMP）水平来促进肌肉舒张，进而参与虹膜平滑肌收缩和舒张的调节。此外，已有证据表明两条途径通过钙信号系统存在联系。在虹膜中，发现血小板活化因子（PAF）通过磷脂酶A2途径而非磷脂酶C途径从磷酸肌醇中释放AA，从而强调了该途径在眼内PG合成中的作用。这些发现表明，眼内虹膜中AA的释放以及PG的合成受到精确调控。在一些物种，如牛、猫和狗中，发现PG可作为完全的钙动员激动剂。除了参与各种钙依赖过程外，PG可能还具有维持静息虹膜平滑肌细胞肌张力的功能。我们的研究表明，PG可能通过增加IP3积累从而促进钙动员，并通过提高cAMP水平来促进肌肉舒张，进而参与虹膜平滑肌收缩和舒张的调节。（摘要截选至400字）
