Yousufzai S Y, Abdel-Latif A A
Prostaglandins. 1984 Sep;28(3):399-415. doi: 10.1016/0090-6980(84)90025-x.
We have investigated the effects of norepinephrine (NE) and acetylcholine (ACh) on prostaglandin (PGE2 and 6 keto-PGF1 alpha) production by rabbit iris, measured by radioimmunoassay (RIA), and the type of phospholipase activated by NE in irides in which phosphatidylinositol (PI) was doubly prelabeled with [3H] myo-inositol and [1-14C] arachidonic acid (14C-AA), quantitated by radiometric and chromatographic methods. PGE2 output in 60 min (3.6 micrograms/g tissue) was 2.6 times greater than 6 keto-PGF1 alpha. PG production is time-dependent and it is stimulated by NE and ACh in a dose-dependent manner. The NE- and ACh-induced release of PGE2, measured by RIA, is mediated through alpha 1-adrenergic and muscarinic cholinergic receptors, respectively, and it requires Ca2+ for maximal stimulation. Studies on the mechanism of AA release from PI in irides doubly prelabeled with 14C-AA and [3H] myo-inositol revealed the following: (a) Both NE and ACh increased the breakdown of PI, and this was accompanied by a significant increase in the release of AA and consequently PGE2. The stimulatory effects of NE and ACh are mediated through alpha 1-adrenergic and muscarinic cholinergic receptors respectively. (b) The NE-induced formation of 3H-lyso PI and the NE-induced metabolism of 14C-1,2-diacyl-glycerol (DG) are time-dependent. Two pathways for AA release from PI are probably operative in the iris: (a) An indirect release by PI-specific phospholipase C which produces DG, followed by the actions of DG- and monoacylglycerol lipases on DG to release AA. (b) A direct release by phospholipase A2. Whether lyso PI is a product of the polyphosphoinositide response remains to be established. Other phospholipids such as phosphatidylcholine and phosphatidylethanolamine could also serve as a source for AA in PG synthesis. In conclusion, the data presented provide evidence that in the iris the neuro-transmitter-stimulated release of PG and AA, from phosphoinositides, for PG synthesis is coupled to the activation of alpha 1-adrenergic and muscarinic cholinergic receptors.
我们通过放射免疫分析法（RIA）研究了去甲肾上腺素（NE）和乙酰胆碱（ACh）对兔虹膜前列腺素（PGE2和6-酮-PGF1α）生成的影响，并通过放射性测量和色谱法对预先用[3H]肌醇和[1-14C]花生四烯酸（14C-AA）双重标记磷脂酰肌醇（PI）的虹膜中NE激活的磷脂酶类型进行了定量分析。60分钟内PGE2的产量（3.6微克/克组织）比6-酮-PGF1α高2.6倍。前列腺素的生成具有时间依赖性，并且受到NE和ACh的剂量依赖性刺激。通过RIA测量，NE和ACh诱导的PGE2释放分别通过α1-肾上腺素能受体和毒蕈碱胆碱能受体介导，并且最大刺激需要Ca2+。对预先用14C-AA和[3H]肌醇双重标记的虹膜中花生四烯酸从PI释放机制的研究表明：（a）NE和ACh均增加了PI的分解，同时伴随着花生四烯酸释放的显著增加，进而导致PGE2释放增加。NE和ACh的刺激作用分别通过α1-肾上腺素能受体和毒蕈碱胆碱能受体介导。（b）NE诱导的3H-溶血磷脂酰肌醇的形成以及NE诱导的14C-1,2-二酰基甘油（DG）的代谢具有时间依赖性。虹膜中花生四烯酸从PI释放可能有两条途径：（a）由PI特异性磷脂酶C间接释放产生DG，随后DG和单酰基甘油脂肪酶作用于DG释放花生四烯酸。（b）由磷脂酶A2直接释放。溶血磷脂酰肌醇是否是多磷酸肌醇反应的产物仍有待确定。其他磷脂如磷脂酰胆碱和磷脂酰乙醇胺也可作为前列腺素合成中花生四烯酸的来源。总之，所呈现的数据提供了证据，表明在虹膜中，神经递质刺激从磷酸肌醇释放前列腺素和花生四烯酸用于前列腺素合成与α1-肾上腺素能受体和毒蕈碱胆碱能受体的激活相关联。
