Gordon R K, Gray R R, Reaves C B, Butler D L, Chiang P K
Walter Reed Army Institute of Research, Department of Applied Biochemistry, Washington DC.
J Pharmacol Exp Ther. 1992 Dec;263(3):997-1002.
Anatoxin-a (ANTX), a nicotinic agonist, has been shown to induce contraction of guinea pig ileum, which was abrogated by the muscarinic antagonist atropine and the nicotinic antagonists tubocurarine and hexamethonium. We showed here that the ganglionic nicotinic antagonist mecamylamine was a better inhibitor of the contraction of ileum induced by ANTX. The sodium channel blocker tetrodotoxin also abolished ANTX-induced contraction. In contrast, alpha-bungarotoxin, the muscle type nicotinic receptor blocker, had no effect on ANTX-induced contraction of guinea pig ileum. Longitudinal muscle-myenteric plexus prepared from guinea pig ileum, labeled with [3H]choline and then incubated with ANTX was shown for the first time to release [3H]acetylcholine (ACh) in a dose-dependent manner. Pretreatment of longitudinal muscle-myenteric plexus with tubocurarine, hexamethonium or mecamylamine blocked ANTX-induced release of [3H]ACh. In contrast, atropine was without effect. Mecamylamine was the most potent antagonist. As observed in ileum contraction, tetrodotoxin completely and potently blocked the release of [3H]ACh induced by ANTX. Neither alpha-bungarotoxin nor the neuromuscular junction blockers conotoxin G1 or M1 could inhibit the [3H]ACh release. Taken together, these results suggested that ANTX activated nicotinic receptors on ganglionic interneurons to trigger a release of ACh, which next stimulated muscarinic receptors and induced ileum contraction.
anatoxin-a（ANTX）是一种烟碱样激动剂，已被证明可诱导豚鼠回肠收缩，而毒蕈碱拮抗剂阿托品以及烟碱拮抗剂筒箭毒碱和六甲铵可消除这种收缩。我们在此表明，神经节烟碱拮抗剂美加明是ANTX诱导的回肠收缩的更好抑制剂。钠通道阻滞剂河豚毒素也可消除ANTX诱导的收缩。相比之下，肌肉型烟碱受体阻滞剂α-银环蛇毒素对ANTX诱导的豚鼠回肠收缩没有影响。首次显示，用[3H]胆碱标记后再与ANTX孵育的豚鼠回肠制备的纵行肌-肠肌丛以剂量依赖性方式释放[3H]乙酰胆碱（ACh）。用筒箭毒碱、六甲铵或美加明预处理纵行肌-肠肌丛可阻断ANTX诱导的[3H]ACh释放。相比之下，阿托品没有作用。美加明是最有效的拮抗剂。如在回肠收缩中观察到的那样，河豚毒素完全且有效地阻断了ANTX诱导的[3H]ACh释放。α-银环蛇毒素以及神经肌肉接头阻滞剂芋螺毒素G1或M1均不能抑制[3H]ACh释放。综上所述，这些结果表明，ANTX激活神经节中间神经元上的烟碱受体以触发ACh释放，随后ACh刺激毒蕈碱受体并诱导回肠收缩。
