EVALUATION OF AN ISOLATED VASCULARLY-PERFUSED RAT STOMACH AS A USEFUL EXPERIMENTAL MODEL FOR STUDIES OF GASTROIINTESTINAL PHARMACOLOGY

我们已经开发了体外实验模型来检测从大鼠胃交感神经释放的非常少量的内源性去甲肾上腺素（NA）（Yokotani，K.et al.，J.Pharmacol.exp.Ther.，1992年）。本研究采用Krebs-Ringer液（胃动脉 * 胃 * 门静脉）灌流大鼠离体胃，观察大鼠离体胃的形态学变化。用电化学法和生物发光法测定灌流液中内源性NA、乙酰胆碱（ACh）和谷氨酸（Glu）的释放量。获得的结果如下。1.高KCl和电刺激迷走神经引起的钙依赖性释放谷氨酸。这种释放被河豚毒素消除。这些结果提供了一个证据，表明谷氨酸作为一种神经递质在胃中。2.电刺激胃交感神经引起NA的钙依赖性释放，然后观察了L、T、N、P、Q和R型通道选择性钙通道阻滞剂对NA释放的影响。N-型通道阻滞剂单独而不是其他有效地消除释放。3.电刺激迷走神经引起ACh的释放。这种释放被μ受体激动剂β-内啡肽阻断，而Xi和chi受体激动剂都没有作用。这些结果提示麻醉性镇痛药对胃的不良反应可能不仅来自中枢作用，而且来自对胃的直接作用。【结论】：离体大鼠胃血管灌流可能是胃药理学研究的一个有用的实验模型。

We have developed experimental in vitro model to detect a very small amount of endogenous noradrenaline (NA) released from the rat gastric sympathetic nerves (Yokotani, K.et al., J.Pharmacol.exp.Ther., 1992). Then, in the present study, we further tried to establish practical availability of this model to elucidate precise mechanism of various gastric disorders and to develope their therapeutics.The isolated rat stomach was perfused with Krebs-Ringer solution (gastric artery*stomach*portal vein). Endogenous NA,acetylcholine (ACh) or glutamate (Glu) released into the perfusate was assayd by electrochmical or bioluminescence method. Results obtained were as follows. 1.Both high KCl and electrical stimulation of the vagus nerve induced a calcium dependent release of Glu. This release was abolished by tetrodotoxin. These results provide an evidence that Glu serves as a neurotransmitter in the stomach. 2.Electrical stimulation of the gastric sympathetic nerve induced a calcium dependent release of NA.Then, effects of various calcium chennel blockers selective to L,T,N,P,Q and R-type channels on this NA release were examined. N-type channel blockers alone but not others are effective to abolish the release. 3.Electrical stimulation of the vagus nerve induced a release of ACh. This release was blocked by a mu receptor agonist, beta-endorphin, while both of xi and chi receptor agonist was without effect. These results suggest that untoward effects of narcotic analgesics on the stomach probably originates from not only central but also direct action to the stomach.{Conclusion} : The isolated vascularly perfused rat stomach is probably a useful experimental model for various pharmacological studies of the stomach.