Releasing mechanisms of acetylcholine from an isolated rat stomach

用改良的Krebs-Ringer溶液测定体外血管灌注大鼠胃内源性乙酰胆碱（ACh）和去甲肾上腺素（NA）溢出。用酶反应和/或高效液相色谱法测定释放到灌注液中的乙酰胆碱和脱氧核糖核酸。2.5 Hz迷走神经刺激诱发的乙酰胆碱溢出可被氧tremorine（毒蕈碱激动剂）抑制，而被阿托品、4-DAMP（M3受体拮抗剂）、甲氧曲明（M2受体拮抗剂）和吡仑西平（M1受体拮抗剂）增强，其效度如下：>甲氧曲明>吡嗪平。可乐定（α -2肾上腺素能受体激动剂）浓度依赖性地降低了诱发的乙酰胆碱溢出，电刺激胃动脉周交感神经（5hz）也抑制了诱发的乙酰胆碱溢出。这种交感抑制乙酰胆碱（α -2肾上腺素受体拮抗剂）可以消除，但吡唑嗪（α -1肾上腺素受体拮抗剂）不能。电刺激含有胃交感神经的动脉周围神经诱发频率依赖性NA溢出。双侧迷走神经刺激（5hz）或氧tremorine可抑制NA溢出。氧tremorine （10 ^<-7> M）诱导的NA溢出抑制作用被阿托品、甲氧曲明、4-DAMP和吡仑西平（效价如下）减弱；阿托品b>甲氧曲明b> 4-DAMP bbb>匹伦西平。这些结果表明，激活毒蕈碱M_2受体可抑制胃交感神经末梢NA的释放，M_3毒蕈碱自受体和α -2肾上腺素受体可抑制胃迷走神经ACh的释放。在胃壁，交感和副交感神经系统的相互作用可能在胃功能的调节中起重要作用。

We measured endogenous acetylcholine (ACh) and noradrenaline (NA) overflow from a vascularly perfused rat stomach in vitro with modified Krebs-Ringer solution. ACh and NA released into the perfusate were electrochemically measured with enzyme reaction and/or high performance liquid chromatography. Evoked ACh overflow by vagal stimulation at 2.5 Hz was inhibited by oxotremorine (muscarinic agonist) and enhanced by atropine, 4-DAMP(M3 receptor antagonist), methoctramine(M2 receptor antagonist) and pirenzepine(M1 receptor antagonist) with the following potency ; atropine > 4-DAMP > methoctramine > pirenzepine. Clonidine (alpha-2 adrenoceptor agonist) concentration-dependently decreased the evoked ACh overflow and electrical stimulation of periarterial gastric sympathetic nerves (5 Hz) also inhibited the evoked ACh overflow. This sympathetic inhibition of ACh overflow was abolished by rauwolscine (alpha-2 adrenoceptor antagonist), but not by prazosin (alpha-1 adrenoceptor antagonist). Electrical stimulation of periarterial nerves containing gastric sympathetic nerves evoked frequency-dependent NA overflow. Bilateral vagus nerve stimulation (5 Hz) or oxotremorine inhibited evoked NA overflow. Oxotremorine (l0^<-7> M)-induced inhibition of NA overflow was attenuated by atropine, methoctramine , 4-DAMP and pirenzepine with the following potency ; atropine > methoctramine > 4-DAMP >> pirenzepine. These results indicate that NA release from gastric sympathetic nerve terminals is inhibited by activation of muscarinic M_2 receptor and that ACh release from gastric vagal nerves is inhibited by M_3 muscarinic autoreceptors and alpha-2 adrenoceptors. In the gastric wall, interaction between sympathetic and parasympathetic nervous systems may play an important role in regulation of gastric functions.