豚鼠回肠毒蕈碱受体的亲和标记

Affinity-labelling of the muscarinic receptor of the guinea-pig illeum.

Lebbin C, Hofmann A, Waser P G

Naunyn Schmiedebergs Arch Pharmacol. 1975;289(3):237-49. doi: 10.1007/BF00499978.

Abstract

The activities of some cholinergic compounds were investigated on the terminal ileum of the guinea-pig and their muscarinic potencies were found to be in the following order: acetylcholine (ACh) greater than diazoacetylcholine (DACh) greater than iodoacetylcholine (IACh) greater than azidoacetylcholine (AACh). 2. Protection experiments with atropine showed a decreased affinity of the four cholinergic compounds for the muscarinic receptor, demonstrating a direct interaction of the drugs and the receptor. 3. The maximal contractions (intrinsic activity) caused by DACh were greater than those casued by ACh, IACh and AACh. 4. Incubation of the ileum with ACh was followed by a reversible loss of its ability to contract (desensitization). The time course of recovery was similiar to that after incubation with AACh. 5. IACh caused a partial (50%), irreversible paralysis of the muscle. 6. The furaziridines seem to react partially irreversibly (30%), whereas paranitrophenyldiazonium fluoborate (p-NDP) caused a complete, irreversible blockade of the muscarinic receptor.

摘要

研究了某些胆碱能化合物对豚鼠回肠末端的作用，发现它们的毒蕈碱活性顺序如下：乙酰胆碱（ACh）＞重氮乙酰胆碱（DACh）＞碘乙酰胆碱（IACh）＞叠氮乙酰胆碱（AACh）。2. 用阿托品进行的保护实验表明，这四种胆碱能化合物与毒蕈碱受体的亲和力降低，证明了药物与受体之间的直接相互作用。3. DACh引起的最大收缩（内在活性）大于ACh、IACh和AACh引起的最大收缩。4. 回肠与ACh孵育后，其收缩能力出现可逆性丧失（脱敏）。恢复的时间进程与与AACh孵育后的相似。5. IACh导致肌肉部分（50%）不可逆麻痹。6. 呋喃氮丙啶似乎发生部分不可逆反应（30%），而对硝基苯基重氮氟硼酸盐（p-NDP）导致毒蕈碱受体完全不可逆阻断。