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Life Sci. 2013 Apr 9;92(12):733-9. doi: 10.1016/j.lfs.2013.01.030. Epub 2013 Feb 9.
To determine if the muscarinic agonist, bethanechol, inhibits the non-cholinergic, atropine-resistant (i.e. putatively purinergic) component of naturally occurring (i.e. reflexogenic) bladder contractions in vivo in the rat, as previously described in vitro. Our second aim was to determine if elevation of endogenous acetylcholine (ACh) with distigmine, an acetylcholine esterase (AChE) inhibitor, could also inhibit non-cholinergic component of reflexogenic bladder contractions.
Cystometry was performed in urethane anesthetized adult female Sprague Dawley rats. The nonselective muscarinic receptor (mAChR) antagonist, atropine, was administered intravenously (i.v.) before and after i.v. administration of the non-selective mAChR agonist, bethanechol, the AChE inhibitor, distigmine or the neurokinin receptor 2 agonist, [βAla(8)]-Neurokinin A(4-10). Intermicturition interval (IMI), bladder contraction amplitude (BCA), postvoid bladder pressure (PVBP), and voiding efficiency (VE) were measured.
Atropine (0.4 mg/kg; n=11 rats) delivered as the first drug, had insignificant effects on BCA (15% reduction) or PVBP (15% increase) and weakly reduced IMI and VE by ~40% (p<0.05) relative to vehicle. Bethanechol and distigmine on their own produced excitatory effects on bladder activity, consistent with mAChR activation. Unexpectedly atropine, administered after bethanechol or after distigmine but not after [βAla(8)]-Neurokinin A(4-10), completely blocked bladder activity for 3-10 min. Partial recovery of bladder activity occurred after that time, but BCA, IMI, and VE remained significantly reduced and PVBP remained significantly increased.
Activation of mAChRs by an exogenous agonist or elevation of endogenous ACh levels by an AChE inhibitor inhibits the non-cholinergic, atropine-resistant, component of reflexogenic bladder contractions in vivo.
确定拟胆碱药氨甲酰甲胆碱是否能抑制体内大鼠自然发生（即反射性）膀胱收缩的非胆碱能、阿托品抵抗（即假定为嘌呤能）成分，如先前在体外所述。我们的第二个目的是确定乙酰胆碱酯酶（AChE）抑制剂毒扁豆碱升高内源性乙酰胆碱（ACh）是否也能抑制反射性膀胱收缩的非胆碱能成分。
在乌拉坦麻醉的成年雌性 Sprague Dawley 大鼠中进行尿动力学检查。在静脉给予非选择性毒蕈碱受体（mAChR）拮抗剂阿托品前后，静脉给予非选择性 mAChR 激动剂氨甲酰甲胆碱、AChE 抑制剂毒扁豆碱或神经激肽受体 2 激动剂[βAla(8)]-神经激肽 A(4-10)。测量排尿间隔（IMI）、膀胱收缩幅度（BCA）、排尿后膀胱压（PVBP）和排尿效率（VE）。
作为第一种药物给予的阿托品（0.4mg/kg；n=11 只大鼠）对 BCA（15%减少）或 PVBP（15%增加）的影响不大，与载体相比，仅轻微降低 IMI 和 VE 约 40%（p<0.05）。氨甲酰甲胆碱和毒扁豆碱本身对膀胱活动产生兴奋作用，与 mAChR 激活一致。出乎意料的是，在给予氨甲酰甲胆碱或毒扁豆碱后，而不是在给予[βAla(8)]-神经激肽 A(4-10)后给予阿托品，完全阻断膀胱活动 3-10 分钟。在此时间后，膀胱活动部分恢复，但 BCA、IMI 和 VE 仍显著降低，PVBP 仍显著升高。
外源性激动剂激活 mAChR 或 AChE 抑制剂升高内源性 ACh 水平可抑制体内反射性膀胱收缩的非胆碱能、阿托品抵抗成分。
