M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder
M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder
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DOI：
10.1152/ajpregu.1998.275.5.r1654
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发表时间：
1998-11-01
影响因子：
2.8
通讯作者：
Ruggieri, MR
中科院分区：
文献类型：
--
作者：
Braverman, AS;Luthin, GR;Ruggieri, MR
在体外膀胱收缩反应的累积卡巴胆碱剂量进行了测量，在选择性毒蕈碱拮抗剂的存在下，从大鼠的主要盆腔神经节双边删除。去神经诱导肥大和超敏感性的膀胱激动剂。对照膀胱对卡巴胆碱诱导的收缩的拮抗作用的亲和力与M-3介导的收缩一致。去神经膀胱中对4-二苯基乙酰氧基-N-甲基哌啶碘甲烷（8.5）和对氟六氢硅地芬尼多（6.6）的亲和力与M-3介导的收缩一致，尽管甲氧四明亲和力（6.5）与M-3介导的收缩一致。毒蕈碱受体的亚型选择性免疫沉淀显示，与正常或假手术对照组相比，去神经膀胱中M-3受体密度总体增加50%，M-3受体密度增加60%，而M-3受体密度没有变化。Mt受体密度的增加与拮抗剂抑制卡巴胆碱诱导的收缩的亲和力的变化一致，并且可能表明M-2受体或M-2和M-3受体的组合直接介导去神经膀胱中的平滑肌收缩。
In vitro bladder contractions in response to cumulative carbachol doses were measured in the presence of selective muscarinic antagonists from rats that had their major pelvic ganglion bilaterally removed. Denervation induced both hypertrophy and a supersensitivity of the bladders to agonist. The affinities in control bladders for antagonism of carbachol-induced contractions were consistent with M-3-mediated contractions. Affinities in denervated bladders for 4-diphenlacetoxy-N-methylpiperidine methiodide (8.5) and p-fluoro hexahydrosilodifenidol (6.6) were consistent with M-3-mediated contractions, although the methoctramine affinity (6.5) was consistent with M-3-mediated contractions. Subtype-selective immunoprecipitation of muscarinic receptors revealed a 50% increase in total and a 60% increase in M-3 receptor density with no change in M-3 receptor density in denervated bladders compared with normal or sham-operated controls. This increase in Mt receptor density is consistent with the change in affinity of the antagonists for inhibition of carbachol-induced contractions and may indicate that M-2 receptors or a combination of M-2 and M-3 receptors directly mediates smooth muscle contraction in the denervated bladder.