Biancani P, Walsh J, Behar J
Gastroenterology. 1985 Oct;89(4):867-74. doi: 10.1016/0016-5085(85)90585-2.
The circular smooth muscle of the rabbit internal anal sphincter, tested in vitro, exhibited spontaneous resting tonus and relaxed with neural stimuli of 0.05-0.5-ms duration and 1-10-Hz frequency. The relaxation was abolished by tetrodotoxin (10(-6) M) but not by atropine or propranolol at the same molar concentration, suggesting that the inhibitory neural fibers mediating relaxation are nonadrenergic and noncholinergic. One-hour incubation in physiologic solution containing 8% of rabbit vasoactive intestinal peptide (VIP) antiserum significantly reduced the relaxation induced by electrical stimulation. The reduction was greater for the shorter duration stimuli, ranging from 80% to 50% for 0.05-ms stimuli to 35%-11% for 0.5-ms stimuli. Control strips were relaxed in a dose-dependent fashion by 10(-9)-10(-6) M VIP; the antiserum at the concentration used completely blocked the relaxation produced by 10(-7) M VIP and reduced the relaxation produced by 10(-6) M VIP. Adenosine triphosphate also relaxed the internal anal sphincter in a dose-dependent manner. Prolonged inhibitory nerve stimulation (0.5 ms, 10 Hz, 30-min train) caused significant reduction in the relaxation induced by exogenous VIP, whereas the relaxation induced by adenosine triphosphate was unaffected. These data are consistent with VIP being an inhibitory neurotransmitter responsible for relaxation of the internal anal sphincter.
对兔肛门内括约肌的环形平滑肌进行体外测试，结果显示其具有自发性静息张力，并在持续时间为0.05 - 0.5毫秒、频率为1 - 10赫兹的神经刺激下松弛。河豚毒素（10⁻⁶ M）可消除这种松弛，但相同摩尔浓度的阿托品或普萘洛尔则不能，这表明介导松弛的抑制性神经纤维是非肾上腺素能和非胆碱能的。在含有8%兔血管活性肠肽（VIP）抗血清的生理溶液中孵育1小时，可显著降低电刺激诱导的松弛。对于较短持续时间的刺激，降低幅度更大，0.05毫秒刺激时从80%降至50%，0.5毫秒刺激时从35%降至11%。对照条带以剂量依赖方式被10⁻⁹ - 10⁻⁶ M的VIP松弛；所用浓度的抗血清完全阻断了10⁻⁷ M VIP产生的松弛，并降低了10⁻⁶ M VIP产生的松弛。三磷酸腺苷也以剂量依赖方式松弛肛门内括约肌。长时间抑制性神经刺激（0.5毫秒，10赫兹，30分钟串刺激）可显著降低外源性VIP诱导的松弛，而三磷酸腺苷诱导的松弛则不受影响。这些数据表明VIP是负责肛门内括约肌松弛的抑制性神经递质。
