Madaus S, Bender H, Schusdziarra V, Kehe K, Munzert G, Weber G, Classen M
Department of Internal Medicine II, Technical University of Munich, F.R.G.
Regul Pept. 1990 Oct 8;30(3):179-92. doi: 10.1016/0167-0115(90)90093-c.
The isolated stomach of rats was vascularly perfused to measure the secretion of gastrin, somatostatin (SLI) and bombesin-like immunoreactivity (BLI). The gastric lumen was perfused with saline pH 7 or pH 2, and electrical vagal stimulation was performed with 1 ms, 10 V and 2, 5 or 10 Hz, respectively. Atropine was added in concentrations of 10(-9) or 10(-7) M to evaluate the role of cholinergic mechanisms. In control experiments, vagal stimulation during luminal pH 2 elicited a significant increase of BLI secretion only at 10 Hz but not at 2 and 5 Hz. Somatostatin release was inhibited independent of the stimulation frequency employed. Gastrin secretion at 2 Hz was twice the secretion rates observed at 5 and 10 Hz, respectively. At luminal pH 7 BLI rose significantly at 5 and 10 Hz. SLI secretion was decreased by all frequencies. Gastrin secretion at 2 and 5 Hz was twice as high as during stimulation with 10 Hz. Atropine at doses of 10(-9), 10(-8), 10(-7) and 10(-6) M had no effect on basal secretion of BLI, SLI and gastrin. At luminal pH 2, atropine increased dose-dependently the BLI response at 2 and 5 but not at 10 Hz. The decrease of SLI during 2 and 5 Hz but not 10 Hz was abolished by atropine 10(-9) M. SLI was reversed to stimulation during atropine 10(-7) M at all frequencies. The rise of gastrin at 2 Hz was reduced by 50%. At luminal pH 7, atropine had comparable effects with a few differences: the BLI response at 10 Hz was augmented and the gastrin response to 2 and 5 Hz was reduced. In conclusion the present data demonstrate a frequency and pH-dependent stimulation of BLI and gastrin release. The stimulation of BLI is predominantly due to atropine-insensitive mechanisms while muscarinic cholinergic mechanisms exert an inhibitory effect on BLI release during lower stimulation frequencies (2 and 5 Hz) independent of the intragastric pH and also during higher frequencies at neutral pH. Both, atropine sensitive and insensitive mechanisms are activated frequency dependent. The atropine-sensitive cholinergic mechanisms but not the noncholinergic mechanisms involved in regulation of G-cell function are pH and frequency dependent. Somatostatin is regulated largely independent of stimulation frequency and pH by at least two pathways involving cholinergic mechanisms of different sensitivity to atropine. These data suggest a highly differentiated regulation of BLI, gastrin and SLI secretion and the interaction between these systems awaits further elucidation.
对大鼠离体胃进行血管灌注，以测量胃泌素、生长抑素（SLI）和蛙皮素样免疫反应性（BLI）的分泌。胃腔用pH 7或pH 2的生理盐水灌注，分别以1毫秒、10伏和2、5或10赫兹进行迷走神经电刺激。加入浓度为10⁻⁹或10⁻⁷M的阿托品，以评估胆碱能机制的作用。在对照实验中，腔内pH 2时迷走神经刺激仅在10赫兹时引起BLI分泌显著增加，而在2和5赫兹时未增加。生长抑素释放不受所用刺激频率的影响。2赫兹时胃泌素分泌分别是5赫兹和10赫兹时观察到的分泌率的两倍。腔内pH 7时，5赫兹和10赫兹时BLI显著升高。所有频率下SLI分泌均减少。2赫兹和5赫兹时胃泌素分泌是10赫兹刺激时的两倍。剂量为10⁻⁹、10⁻⁸、10⁻⁷和10⁻⁶M的阿托品对BLI、SLI和胃泌素的基础分泌无影响。腔内pH 2时，阿托品剂量依赖性地增加2赫兹和5赫兹时的BLI反应，但不增加10赫兹时的反应。10⁻⁹M阿托品消除了2赫兹和5赫兹（而非10赫兹）时SLI的减少。10⁻⁷M阿托品在所有频率下使SLI转变为受刺激状态。2赫兹时胃泌素的升高降低了50%。腔内pH 7时，阿托品有类似作用，但有一些差异：10赫兹时的BLI反应增强，2赫兹和5赫兹时的胃泌素反应减弱。总之，目前的数据表明BLI和胃泌素释放存在频率和pH依赖性刺激。BLI的刺激主要归因于对阿托品不敏感的机制，而毒蕈碱胆碱能机制在较低刺激频率（2和5赫兹）时对BLI释放发挥抑制作用，与胃内pH无关，在中性pH的较高频率时也如此。对阿托品敏感和不敏感的机制均按频率依赖性被激活。参与G细胞功能调节的对阿托品敏感的胆碱能机制而非非胆碱能机制是pH和频率依赖性的。生长抑素在很大程度上通过至少两条涉及对阿托品敏感性不同的胆碱能机制的途径，独立于刺激频率和pH进行调节。这些数据表明BLI、胃泌素和SLI分泌存在高度分化的调节，这些系统之间的相互作用有待进一步阐明。
