PHYSIOLOGY AND PHARMACOLOGY OF PROSTAGLANDINS
PHYSIOLOGY AND PHARMACOLOGY OF PROSTAGLANDINS
复制标题
DOI：
10.1007/bf01309317
复制
发表时间：
1986-02-01
影响因子：
3.1
通讯作者：
PAWLIK, W
中科院分区：
文献类型：
--
作者：
KONTUREK, SJ;PAWLIK, W
前列腺素 (PG) 是多不饱和酸代谢的产物，特别是在磷脂酶 A2 的作用下，响应各种物理、化学和神经激素因素，从膜磷脂中释放花生四烯酸 (AA)。 AA 通过两种不同的酶促途径快速代谢为含氧产物：环氧合酶和脂氧合酶。中间环加氧酶产物转化为初级PG，而脂加氧酶产物转化为白三烯。各种环氧合酶产物的产生因组织而异。阿司匹林和相关抗炎药会减少所有环氧合酶产物的组织生物合成；它们的治疗作用和副作用与环氧合酶的抑制作用平行。外源性 PG 表现出广泛的作用。 E系列和PGI2的PG由内皮和血管壁产生，以维持微循环并抵消血栓素A2(TXA2)的血管收缩和促聚集作用。 E 和 I 系列的外源性 PG 是各种血管床中的有效血管扩张剂，可降低全身血压并反射性刺激心率。 PGE 和 PGI2 增加肾血流量并引起利尿和尿钠排泄，部分是通过调节肾素-血管紧张素-醛固酮系统来实现的。 PGF 收缩支气管和肠道肌肉，而 PGE 和 PGI2 则具有相反的作用。 PGE 和 PGF（而非 PGI2）会引起子宫肌肉强烈收缩，因此产生不良的子宫收缩作用。 PGE 可以放松支气管肌肉，而 PGF 则可以引起支气管收缩；它们的不平衡可能导致支气管哮喘的支气管张力增高。 E系列和I系列的PG以及TXA2由胃肠粘膜产生，并在神经或激素刺激下释放到管腔中；它们可能参与维持粘膜完整性和微循环。 E和I系列的外源性PG抑制胃酸分泌并刺激碱性分泌，同时增加粘膜血流量。所有 PG，包括那些对酸分泌无抑制作用的 PG，都对各种溃疡原和坏死剂具有细胞保护作用。经典的 PG 仅构成 AA 代谢生物活性产物的一小部分，最近对脂氧合酶产物的研究强调了它们的生物活性并参与多种病理状况。
Prostaglandins (PGs) are products of polyunsaturated acid metabolism, particularly arachidonic acid (AA) released from membrane phospholipids by the action of phospholipase A2in response to a variety of physical, chemical, and neurohormonal factors. AA is rapidly metabolized to oxygenated products by two distinct enzymatic pathways: cyclooxygenase and lipoxygenase. The intermediate cyclooxygenase products are converted to primary PGs, while the lipoxygenase products are converted to leukotrienes. The generation of various cyclooxygenase products varies from tissue to tissue. Aspirin and related antiinflammatory drugs reduce tissue biosynthesis of all cyclooxygenase products; their therapeutic effects and side effects parallel the inhibition of cyclooxygenase. Exogenous PGs exhibit a broad spectrum of effects. PGs of the E series and PGI2are generated by the endothelium and the vessel wall to maintain the microcirculation and to counteract the vasoconstrictive and proaggregatory actions of thromboxane A2(TXA2). Exogenous PGs of the E and I series are potent vasodilators in various vascular beds, and result in decreased systemic blood pressure and reflex stimulation of heart rate. PGEs and PGI2increase renal blood flow and provoke diuresis and natriuresis, partly by modulating the renin-angiotensin-aldosterone system. PGFs contract the bronchial and gut muscle, while PGEs and PGI2have opposite effects. PGEs and PGFs, but not PGI2, cause a strong contraction of the uterine muscle, hence their undesirable uterotonic effects. PGEs relax bronchial muscle, whereas PGFs cause bronchoconstriction; their imbalance may contribute to the high bronchial tone in bronchial asthma. PGs of the E and I series and TXA2are generated by the gastrointestinal mucosa and released into the lumen upon neural or hormonal stimulation; they probably participate in the maintenance of mucosal integrity and microcirculation. Exogenous PGs of the E and I series inhibit gastric acid secretion and stimulate alkaline secretion while increasing mucosal blood flow. All PGs, including those noninhibitory for acid secretion, are cytoprotective against various ulcerogens and necrotizing agents. The classic PGs constitute only a small fraction of biologically active products of AA metabolism, and recent studies on the lipoxygenase products emphasize their biological activity and involvement in a variety of pathological conditions.