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[肾上腺素能受体与α2激动剂——2:通过基因敲除小鼠和基因敲低大鼠对肾上腺素能受体亚型的功能分析]

[Adrenergic receptor and alpha 2 agonist--2: Function analysis of adrenoceptor subtype by knockout mice and knockdown rats].

作者信息

Mizobe T

机构信息

Department of Anesthesiology, Kyoto Prefectural, University of Medicine.

出版信息

Masui. 1997 Jul;46(7):934-41.

PMID:9251508
Abstract

Alpha 2 adrenergic agonists will soon be used in the anesthetic management for their sedative/hypnotic, anesthetic-sparing, analgesic and sympatholytic properties. But the clinically available alpha 2 agonists have unwanted side-effects such as acute hypertension and bradycardia following a bolus injection because these agonists do not discriminate between the 3 alpha 2 adrenoceptor subtypes. Molecular biological methods can identify mediating receptor subtype for each response. Knockout mice study reveals that the alpha 2 B adrenoceptor subtype mediates the hypertensive response to alpha 2 agonists. Knockdown study using the antisense technology demonstrates that the alpha 2 A adrenoceptor subtype mediates the hypnotic and analgesic effects of alpha 2 agonists. The next generation of alpha 2 agonists should be alpha 2 A selective to maximize anesthetic and analgesic effects while minimizing hypertensive response.

摘要

α2肾上腺素能激动剂因其镇静/催眠、节省麻醉药、镇痛和抗交感神经特性,很快将用于麻醉管理。但临床上可用的α2激动剂存在不良副作用,如单次静脉注射后出现急性高血压和心动过缓,因为这些激动剂无法区分3种α2肾上腺素能受体亚型。分子生物学方法可识别每种反应的介导受体亚型。基因敲除小鼠研究表明,α2B肾上腺素能受体亚型介导α2激动剂的高血压反应。使用反义技术的基因敲低研究表明,α2A肾上腺素能受体亚型介导α2激动剂的催眠和镇痛作用。下一代α2激动剂应具有α2A选择性,以最大程度地发挥麻醉和镇痛作用,同时最小化高血压反应。

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