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

我们建立了体外实验模型，以检测大鼠胃交感神经释放的极少量内源性去甲肾上腺素（NA） （Yokotani， K.et al.， J.Pharmacol.exp.Ther.）。, 1992)。因此，在本研究中，我们进一步尝试建立该模型的实际可用性，以阐明各种胃疾病的确切机制并开发其治疗方法。取离体大鼠胃灌注克雷布斯-林格液（胃动脉*胃*门静脉）。用电化学或生物发光法测定灌注液中释放的内源性NA、乙酰胆碱（ACh）或谷氨酸（Glu）。所得结果如下：1.高钾离子和电刺激迷走神经均可诱导谷氨酸的钙依赖性释放。这种释放被河豚毒素所消除。这些结果为谷氨酸在胃中作为一种神经递质提供了证据。2.电刺激胃交感神经诱导NA的钙依赖性释放。然后，研究了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。只有n型通道阻滞剂才能有效消除释放。3.电刺激迷走神经引起乙酰胆碱的释放。这种释放被mu受体激动剂-内啡肽阻断，而xi和chi受体激动剂均无效果。这些结果表明，麻醉性镇痛药对胃的不良影响可能不仅源于中枢作用，而且源于直接作用于胃。{结论}：离体血管灌注大鼠胃可能是一个有用的胃药理研究的实验模型。

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.