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用于评估β2-肾上腺素受体介导活性的豚鼠子宫和大鼠输精管制剂的比较。

Comparison of guinea pig uterine and rat vas deferens preparations for assessment of beta 2-adrenoceptor-mediated activity.

作者信息

Krstew E, Malta E, Raper C

出版信息

J Pharmacol Methods. 1982 Dec;8(4):279-89. doi: 10.1016/0160-5402(82)90045-6.

Abstract

In the present study, investigations were performed to determine the subtype(s) of beta-receptor-mediating relaxation in K+-depolarized guinea pig uterine preparations, and inhibition of twitches in field-stimulated rat vas deferens preparations. The relative activities of (-)-isoprenaline, salbutamol, terbutaline, noradrenaline, and RO363, and the affinity constants determined for the beta 1-receptor antagonist atenolol, and the beta 2-receptor antagonist lCl 118551, indicated that all the inhibitory responses in both preparations were mediated solely through beta 2-adrenoceptor stimulation. In the uterine preparations there was a small population of alpha-receptors which were of little consequence when assessing beta 2-receptor-mediated activity. During K+-induced contractures, both neuronal and extraneuronal uptake systems were inactivated. In rat vas deferens preparations, it was necessary to pretreat the tissues with phenoxybenzamine in order to prevent alpha-receptor actions and neuronal and extraneuronal uptake systems interfering with beta-receptor-mediated activity. In both tissues, 6-8 highly reproducible concentration-effect curves to (-)-isoprenaline could be established. However, the uterine preparation responded more robustly to repeated washings, required less sensitive recording apparatus, and showed responses to individual concentrations of drugs that were more readily quantified. However, in general, both preparations appear to be suitable as tissues for assessing the beta 2-adrenoceptor actions of drugs.

摘要

在本研究中,开展了多项实验,以确定在钾离子去极化的豚鼠子宫标本中介导舒张的β受体亚型,以及在电场刺激的大鼠输精管标本中抑制抽搐的情况。(-)-异丙肾上腺素、沙丁胺醇、特布他林、去甲肾上腺素和RO363的相对活性,以及针对β1受体拮抗剂阿替洛尔和β2受体拮抗剂ICI 118551测定的亲和常数,表明两种标本中的所有抑制反应均仅通过β2肾上腺素能受体刺激介导。在子宫标本中,存在少量α受体,在评估β2受体介导的活性时其影响不大。在钾离子诱导的挛缩过程中,神经元和非神经元摄取系统均失活。在大鼠输精管标本中,有必要用酚苄明对组织进行预处理,以防止α受体作用以及神经元和非神经元摄取系统干扰β受体介导的活性。在两种组织中,均可建立6 - 8条对(-)-异丙肾上腺素高度可重复的浓度-效应曲线。然而,子宫标本对重复冲洗反应更强,所需的记录设备灵敏度较低,并且对单个药物浓度的反应更易于量化。不过,总体而言,两种标本似乎都适合作为评估药物β2肾上腺素能受体作用的组织。

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