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前列腺素受体特性的研究:一项拟议的分类法。

Studies on the characterisation of prostanoid receptors: a proposed classification.

作者信息

Kennedy I, Coleman R A, Humphrey P P, Levy G P, Lumley P

出版信息

Prostaglandins. 1982 Nov;24(5):667-89. doi: 10.1016/0090-6980(82)90036-3.

Abstract

Comparison of rank orders of agonist potency of the naturally occurring prostanoids, PGD2, PGE2, PGF2 alpha and PGI2 as well as the stable TxA2 mimetic, U-46619, on a range of smooth muscle preparations provides evidence for the existence of distinct receptors for PGE2, PGF2 alpha and TxA2. Since others have provided evidence for the existence of distinct receptors for PGD2 and PGI2, we suggest that receptors exist for each of these naturally occurring 2-series prostanoids. Results obtained with two specific prostanoid receptor blocking drugs, SC-19220 and AH 19437, support and extend these conclusions. SC-19220 selectively blocks some but not all PGE-sensitive receptors, while AH 19437 selectively blocks all U-46619/TxA2-sensitive receptors. A nomenclature for prostanoid receptors is proposed, in which each receptor is designated the letter P preceded by a letter signifying the most potent natural prostanoid agonist at that receptor, such that receptors sensitive to PGs D2, E2, F2 alpha, I2 and TxA2 become DP-, EP-, FP-, IP and TP- receptors respectively. Where some sub-division is required within a receptor group, e.g. EP-receptors (SC-19220-sensitive and SC-19220-insensitive), subscript numbers may be used such that these are EP1 and EP2 subtypes. The resulting scheme is a working hypothesis and its confirmation requires the development of potent selective prostanoid receptor blocking drugs for each postulated type.

摘要

天然存在的前列腺素PGD2、PGE2、PGF2α和PGI2以及稳定的血栓素A2类似物U-46619在一系列平滑肌制剂上的激动剂效力等级顺序比较,为PGE2、PGF2α和血栓素A2存在不同受体提供了证据。由于其他人已为PGD2和PGI2存在不同受体提供了证据,我们认为这些天然存在的2-系列前列腺素各自都存在受体。用两种特异性前列腺素受体阻断药物SC-19220和AH 19437获得的结果支持并扩展了这些结论。SC-19220选择性阻断部分而非全部对PGE敏感的受体,而AH 19437选择性阻断所有对U-46619/血栓素A2敏感的受体。提出了一种前列腺素受体命名法,其中每个受体被指定为字母P,前面加上一个字母,表示该受体上最有效的天然前列腺素激动剂,这样对PGs D2、E2、F2α、I2和血栓素A2敏感的受体分别成为DP-、EP-、FP-、IP和TP-受体。在一个受体组内需要一些细分时,例如EP-受体(对SC-19220敏感和对SC-19220不敏感),可以使用下标数字,即这些是EP1和EP2亚型。由此产生的方案是一个工作假设,其证实需要为每种假定类型开发有效的选择性前列腺素受体阻断药物。

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