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[前列腺素生物学及其治疗学意义]

[Biology of prostaglandins with reference to therapeutic aspects].

作者信息

Losert W

出版信息

Arzneimittelforschung. 1975 Feb;25(2):135-48.

PMID:164200
Abstract

Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired "target" tissues are available.

摘要

前列腺素是具有多种生物活性的不饱和脂肪酸的高效衍生物。到目前为止,几乎在所有研究过的组织中都能合成和代谢前列腺素。E型和F型前列腺素可被视为激素对细胞功能影响的局部调节剂,在某些情况下(肾脏、子宫 - 黄体)可视为局部或组织激素。因此,它们似乎参与神经传递、肾功能、脂肪组织中甘油三酯代谢和孕酮生物合成的调节。除了对肾血流量的影响外,A型前列腺素可能还具有作为调节血压的循环激素的额外功能。介导大多数非甾体激素作用的第二信使系统(环磷酸腺苷、钙离子 - 环磷酸鸟苷)也参与前列腺素的作用,至少是E型和F型前列腺素的作用。前列腺素代谢紊乱(生物合成增加或减少)被认为在炎症、疼痛、发热、高血压、支气管哮喘以及胃或十二指肠溃疡形成的发病机制中起作用。具有抗炎、镇痛和解热活性的药物已被证明是前列腺素形成的有效抑制剂。由于前列腺素具有大量导致不良副作用的生物作用,长期以来,局部前列腺素缺乏或通过给予外源性化合物(天然前列腺素或修饰衍生物)对前列腺素单一效应进行治疗性应用的相关性一直不太令人满意。在成功诱导治疗性流产方面已获得了广泛经验。这种作用基于E型和F型前列腺素对妊娠子宫平滑肌的刺激作用,而妊娠子宫平滑肌对其他刺激(如催产素)的影响具有抗性。在此,通过向子宫腔内局部给予低剂量前列腺素可降低副作用的发生率。然而,只有当有对所需“靶”组织具有更特异性作用的修饰衍生物时,前列腺素的治疗效用才能得到普遍提高。

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