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The Innervation of the Pelvic and adjoining Viscera: Part II. The Bladder. Part III. The External Generative Organs. Part IV. The Internal Generative Organs. Part V. Position of the Nerve Cells on the Course of the Efferent Nerve Fibres.盆腔及相邻脏器的神经支配:第二部分。膀胱。第三部分。外生殖器。第四部分。内生殖器。第五部分。传出神经纤维行程上神经细胞的位置。
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The use of the slowly degradable analog, alpha, beta-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder.使用缓慢降解类似物α,β-亚甲基ATP诱导P2嘌呤受体脱敏:对豚鼠膀胱非肾上腺素能、非胆碱能反应的影响
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Purinergic receptors: photoaffinity analog of adenosine triphosphate is a specific adenosine triphosphate antagonist.嘌呤能受体:三磷酸腺苷的光亲和类似物是一种特异性三磷酸腺苷拮抗剂。
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Atropine-resistant excitatory junction potentials in rabbit bladder are blocked by alpha,beta-methylene ATP.α,β-亚甲基三磷酸腺苷可阻断兔膀胱中对阿托品耐受的兴奋性突触后电位。
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P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2y-but not the P2x-purinoceptor.兔肠系膜动脉中两种亚型的P2嘌呤受体:活性蓝2选择性抑制通过P2Y嘌呤受体而非P2X嘌呤受体介导的反应。
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The effect of arylazido aminopropionyl ATP (ANAPP3) on inhibition of pelvic nerve evoked contractions of the cat urinary bladder.芳基叠氮氨基丙酰ATP(ANAPP3)对猫膀胱盆神经诱发收缩的抑制作用。
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PPADS可选择性拮抗兔膀胱中P2X嘌呤受体介导的反应。

PPADS selectively antagonizes P2X-purinoceptor-mediated responses in the rabbit urinary bladder.

作者信息

Ziganshin A U, Hoyle C H, Bo X, Lambrecht G, Mutschler E, Bäumert H G, Burnstock G

机构信息

Department of Anatomy and Developmental Biology, University College London.

出版信息

Br J Pharmacol. 1993 Dec;110(4):1491-5. doi: 10.1111/j.1476-5381.1993.tb13990.x.

DOI:10.1111/j.1476-5381.1993.tb13990.x
PMID:8306091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175839/
Abstract
  1. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), an inhibitor of P2X-purinoceptor-mediated responses in rabbit vas deferens, was investigated for its ability to antagonize contractions evoked by alpha,beta-methylene ATP (alpha,beta-MeATP), carbachol and electrical field stimulation in the rabbit urinary bladder detrusor muscle. 2. PPADS. (1-30 microM) caused concentration-dependent inhibition of contractions to the stable P2X-purinoceptor agonist, alpha,beta-MeATP, decreasing the maximum response to alpha,beta-MeATP (30 microM) at concentrations of 3-30 microM. The pD2 value for alpha,beta-MeATP in the absence of PPADS was 6.52 +/- 0.10 (8). In the presence of PPADS at concentrations of 1, 3, 10 and 30 microM the negative log concentrations of alpha,beta-MeATP that cause the same contractile response as the pD2 value were significantly different from control, being respectively 6.17 +/- 0.09 (8), 5.64 +/- 0.12 (7), 5.15 +/- 0.23 (7) and 4.78 +/- 0.22 (5). 3. PPADS (1-30 microM) caused concentration-dependent inhibition of contractions to stimulation of intramural purinergic nerves (1-32 Hz). There was a greater inhibition at lower frequencies (1-8 Hz) than at higher frequencies (16-32 Hz). PPADS, 30 microM, did not produce significantly greater antagonism than 10 microM. 4. PPADS (30 microM) had no significant influence on the contractile potency of carbachol: the pD2 values of carbachol in the absence and presence of PPADS were not significantly different being 6.42 +/- 0.16 (5) and 6.33 +/- 0.18 (5), respectively. However, PPADS caused a small, but significant, suppression of the maximal response of carbachol, reducing it by approximately 9%. 5. Radioligand binding studies carried out on rabbit bladder membranes with [3H]-alpha,beta-methylene ATP([3H]-alpha,beta-MeATP) showed that PPADS concentration-dependently inhibited the binding of [3H]-alpha,beta-MeATP to P2X-purinoceptors, while the binding of [3H]-quinuclidinyl benzilate to muscarinic cholinoceptors was not affected.6. Thus, PPADS (1-30 microM) antagonized responses mediated via P2X-purinoceptors in the rabbit urinary bladder. It was selective for P2-purinoceptor-mediated contractions rather than those mediated via muscarinic receptors. Binding studies demonstrated that the antagonistic effect of PPADS is via a direct interaction with P2x-purinoceptors.
摘要
  1. 研究了磷酸吡哆醛-6-偶氮苯-2',4'-二磺酸(PPADS),一种兔输精管中P2X嘌呤受体介导反应的抑制剂,考察其拮抗α,β-亚甲基ATP(α,β-MeATP)、卡巴胆碱和电场刺激诱发兔膀胱逼尿肌收缩的能力。2. PPADS(1 - 30微摩尔)对稳定的P2X嘌呤受体激动剂α,β-MeATP诱发的收缩产生浓度依赖性抑制,在3 - 30微摩尔浓度下降低对α,β-MeATP(30微摩尔)的最大反应。无PPADS时α,β-MeATP的pD2值为6.52±0.10(8)。在1、3、10和30微摩尔浓度的PPADS存在下,引起与pD2值相同收缩反应的α,β-MeATP的负对数浓度与对照有显著差异,分别为6.17±0.09(8)、5.64±0.12(7)、5.15±0.23(7)和4.78±0.22(5)。3. PPADS(1 - 30微摩尔)对壁内嘌呤能神经刺激(1 - 32赫兹)诱发的收缩产生浓度依赖性抑制。低频(1 - 8赫兹)时的抑制作用大于高频(16 - 32赫兹)。30微摩尔的PPADS产生的拮抗作用并不比10微摩尔时显著更强。4. PPADS(30微摩尔)对卡巴胆碱的收缩效力无显著影响:无PPADS和有PPADS时卡巴胆碱的pD2值无显著差异,分别为6.42±0.16(5)和6.33±0.18(5)。然而,PPADS对卡巴胆碱的最大反应有轻微但显著的抑制,使其降低约9%。5. 用[3H]-α,β-亚甲基ATP([3H]-α,β-MeATP)对兔膀胱膜进行的放射性配体结合研究表明,PPADS浓度依赖性抑制[3H]-α,β-MeATP与P2X嘌呤受体的结合,而[3H]-喹核醇基苯甲酸酯与毒蕈碱胆碱受体的结合未受影响。6. 因此,PPADS(1 - 30微摩尔)拮抗兔膀胱中通过P2X嘌呤受体介导的反应。它对P2嘌呤受体介导的收缩具有选择性,而非对通过毒蕈碱受体介导的收缩。结合研究表明,PPADS的拮抗作用是通过与P2X嘌呤受体直接相互作用实现的。