M3 muscarinic receptors but not M2 mediate contraction of the porcine detrusor muscle in vitro.
M3 muscarinic receptors but not M2 mediate contraction of the porcine detrusor muscle in vitro.
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DOI：
10.1046/j.1365-2680.2000.00181.x
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发表时间：
2000-06
期刊：
影响因子：
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通讯作者：
D. Sellers;T. Yamanishi;C. Chapple;C. Couldwell;K. Yasuda;R. Chess-Williams
中科院分区：
文献类型：
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作者：
D. Sellers;T. Yamanishi;C. Chapple;C. Couldwell;K. Yasuda;R. Chess-Williams
1.本研究的目的是确定毒蕈碱受体亚型介导的猪逼尿肌平滑肌在体外收缩的作用。2.将猪逼尿肌条置于生理盐水中，记录其张力变化。在不存在和存在一系列毒蕈碱拮抗剂（4-DAMP，甲氧曲明，达非那新，奥昔布宁，托特罗定和哌仑西平）的情况下获得对卡巴胆碱的反应。计算拮抗剂亲和力值（pKB值），并与文献中引用的这些拮抗剂在每种毒蕈碱受体亚型的亲和力值进行比较。3. M3选择性拮抗剂4-DAMP和达非那新具有高亲和力（pKB值分别为9.4和8.6）。奥昔布宁、托特罗定和哌仑西平的亲和力分别为8.2、8.1和6.8，而M2选择性试剂甲氧四明的亲和力相对较低（pKB = 6.1）。因此，对猪逼尿肌的亲和力的排序为4-DAMP >达非那新>奥昔布宁>托特罗定>哌仑西平>甲氧四明。将在膀胱上获得的拮抗剂亲和力与已发表的这些拮抗剂在五种毒蕈碱受体亚型上的亲和力进行相关性分析，确定M3（m3）受体是介导体外逼尿肌收缩反应的毒蕈碱亚型。4.这些数据表明，一小群M3-毒蕈碱受体必须介导猪逼尿肌在体外对毒蕈碱受体刺激的直接收缩反应。
1. The objective of the study was to determine the role of muscarinic receptor subtypes in mediating contraction of the porcine detrusor smooth muscle in vitro. 2. Strips of pig detrusor muscle were set up in physiological salt solution and the tensions developed by the tissues were recorded. Responses to carbachol were obtained in the absence and presence of a range of muscarinic antagonists (4-DAMP, methoctramine, darifenacin, oxybutynin, tolterodine and pirenzepine). Antagonist affinity values (pKB values) were calculated and compared with those quoted in the literature for these antagonists at each of the muscarinic receptor subtypes. 3. The M3-selective antagonists, 4-DAMP and darifenacin had high affinities (pKB values of 9.4 and 8.6, respectively). Oxybutynin, tolterodine and pirenzepine had affinities of 8.2, 8.1 and 6.8, respectively, whilst the M2-selective agent methoctramine had a relatively low affinity (pKB = 6.1). The rank order of affinities was, therefore, 4-DAMP > darifenacin > oxybutynin > tolterodine > pirenzepine > methoctramine for the pig detrusor. Correlation of the antagonist affinities obtained on the bladder with those published for these antagonists at the five muscarinic receptor subtypes identified the M3(m3)-receptor as the muscarinic subtype mediating detrusor contractile responses in vitro. 4. These data suggest that a small population of M3-muscarinic receptors must mediate direct contractile responses of the pig detrusor muscle to muscarinic receptor stimulation in vitro.