Brown D A, Fatherazi S, Garthwaite J, White R D
Br J Pharmacol. 1980 Dec;70(4):577-92. doi: 10.1111/j.1476-5381.1980.tb09777.x.
1 Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic-receptor agonists were recorded by an extracellular ;air-gap' method.2 Muscarinic agonists produced a delayed low-amplitude ganglion depolarization, frequently preceded by a hyperpolarization. Potentials were enhanced by reducing K(+) or Ca(2+).3 Mean ED(50) values (muM) for depolarization at 25 degrees C were: oxotremorine 0.004, methylfurmethide 0.11, (+/-)-muscarine 0.24, furmethide 1.56, pilocarpine 4.81 and AHR-602 (N-benzylpyrrolidylacetate methobromide) 10.8. Responses produced by oxotremorine, pilocarpine and AHR-602 showed some characteristics of ;partial agonism'. ED(50) values (muM) for choline esters (measured in the presence of 2.5 mM hexamethonium) were: acetylcholine 3.2, methacholine 59 and bethanechol 78.4 Responses to muscarine were antagonized by hyoscine (K(I) 0.49 nM) atropine (K(I) 0.24 nM) methylscopolamine (K(I) 0.09 nM) lachesine (K(I) 0.15 nM) and (weakly) by hexamethonium (K(I) 0.2 mM). Propylbenzilylcholine mustard produced irreversible antagonism with an apparent onset rate constant of 2 x 10(5) M(-1)S(-1).5 Depolarization was accompanied by facilitation of submaximal ganglionic transmission.6 Muscarine (1 to 100 muM) initially reduced, then increased, the rate of (86)Rb(+)-efflux from isolated ganglia at both 6 and 120 mM K(+). These effects were reduced by 1 muM hyoscine.7 No consistent change in the amounts of cyclic 3',5'-guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.8 Mean against ED(50) values (muM) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (+/-)-muscarine 0.48, pilocarpine 7.8 and AHR-602 9.9. Mean antagonist K(I) values (nM) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27.9 It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED(50) and antagonist K(I) values, and that the major difference between them lies in the greater ;efficacy' of certain agonists (pilocarpine, AHR-602 and McN-A-343) on the ganglion.
采用细胞外“气隙”法记录毒蕈碱受体激动剂对大鼠离体颈上神经节产生的电位变化。
毒蕈碱激动剂可引起延迟的低幅度神经节去极化，常先出现超极化。降低细胞外钾离子浓度或钙离子浓度可增强该电位。
25℃时去极化的平均半数有效浓度（μM）分别为：氧化震颤素0.004、甲基呋氨甲酰胆碱0.11、（±）-毒蕈碱0.24、呋氨甲酰胆碱1.56、毛果芸香碱4.81和AHR - 602（N - 苄基吡咯烷基乙酸甲酯溴化物）10.8。氧化震颤素、毛果芸香碱和AHR - 602产生的反应表现出“部分激动”的一些特征。胆碱酯类药物的半数有效浓度（μM）（在2.5 mM六甲铵存在下测定）分别为：乙酰胆碱3.2、醋甲胆碱59和氨甲酰甲胆碱78。
毒蕈碱的反应可被东莨菪碱（抑制常数0.49 nM）、阿托品（抑制常数0.24 nM）、甲基东莨菪碱（抑制常数0.09 nM）、拉切辛（抑制常数0.15 nM）以及（较弱地）被六甲铵（抑制常数0.2 mM）拮抗。丙基苯甲酰胆碱氮芥产生不可逆拮抗作用，表观起始速率常数为2×10⁵ M⁻¹S⁻¹。
去极化伴随着次最大神经节传递的易化。
毒蕈碱（1至100 μM）最初降低，然后增加，在6 mM和120 mM细胞外钾离子浓度下，离体神经节中⁸⁶Rb⁺外流速率。这些作用可被1 μM东莨菪碱减弱。
未检测到毒蕈碱去极化伴随的离体神经节中3',5'-环磷酸鸟苷含量的一致变化。
收缩大鼠离体回肠的平均半数有效浓度（μM）分别为：氧化震颤素0.012、甲基呋氨甲酰胆碱0.29、（±）-毒蕈碱0.48、毛果芸香碱7.8和AHR - 602 9.9。平均拮抗剂抑制常数（nM）分别为：东莨菪碱0.17、阿托品0.34和拉切辛0.27。
得出结论，就激动剂半数有效浓度和拮抗剂抑制常数而言，神经节毒蕈碱受体与回肠受体非常相似，它们之间的主要差异在于某些激动剂（毛果芸香碱、AHR - 602和McN - A - 343）对神经节具有更大的“效能”。
