Kuwahara A, Tien X Y, Wallace L J, Cooke H J
J Pharmacol Exp Ther. 1987 Aug;242(2):600-6.
This study examined the role of cholinergic receptors in mediating the chloride secretory response evoked by stimulation of enteric neurons in muscle-stripped segments of mucosa from guinea pig distal colon set up in flux chambers. Basal short-circuit current was not altered by tetrodotoxin, hexamethonium or muscarinic antagonists. The neurally evoked response was not altered by hexamethonium, but was reduced by muscarinic antagonists with a rank order of potency: atropine = 4-diphenyl acetoxy-N-methylpiperidine greater than pirenzepine. 1,1-Dimethyl-4-phenyl-piperazinium iodide increased resting short-circuit current above basal levels. Carbachol and bethanechol evoked a concentration-dependent increase in short-circuit current that was reduced by tetrodotoxin. The effects of carbachol were antagonized by hexamethonium, 4-diphenyl acetoxy-N-methylpiperidine and pirenzepine. Competition for [3H]quinuclidinyl benzilate binding indicated a rank order of potency of 4-diphenyl acetoxy-N-methylpiperidine greater than pirenzepine greater than carbachol greater than bethanechol. These studies indicate that cholinergic and noncholinergic transmission play a significant role in regulation of chloride transport in the guinea pig distal colon. Both nicotinic and muscarinic receptors on neurons that project to the mucosa as well as epithelial muscarinic receptors are mediators of the chloride secretory response.
本研究检测了胆碱能受体在介导豚鼠远端结肠黏膜肌层剥除段置于通量室中，刺激肠神经元所诱发的氯离子分泌反应中的作用。河豚毒素、六甲铵或毒蕈碱拮抗剂均未改变基础短路电流。六甲铵未改变神经诱发反应，但毒蕈碱拮抗剂可降低该反应，其效力顺序为：阿托品 = 4-二苯基乙酰氧基-N-甲基哌啶＞哌仑西平。碘化1,1-二甲基-4-苯基哌嗪使静息短路电流高于基础水平。卡巴胆碱和氯贝胆碱可引起短路电流浓度依赖性增加，该增加被河豚毒素降低。卡巴胆碱的作用被六甲铵、4-二苯基乙酰氧基-N-甲基哌啶和哌仑西平拮抗。对[³H]喹核醇基苯甲酸酯结合的竞争表明效力顺序为：4-二苯基乙酰氧基-N-甲基哌啶＞哌仑西平＞卡巴胆碱＞氯贝胆碱。这些研究表明，胆碱能和非胆碱能传递在豚鼠远端结肠氯离子转运调节中起重要作用。投射至黏膜的神经元上的烟碱样和毒蕈碱样受体以及上皮毒蕈碱样受体均为氯离子分泌反应的介质。
