Zheng J L, Bian C F, Qin W, Yu A Y
Department of Pharmacology, Xuzhou Medical College, China.
Zhongguo Yao Li Xue Bao. 1992 Jul;13(4):349-54.
Radioreceptor binding assays using [3H]quinuclidinyl benzilate and [3H]pirenzepine were performed on the pons and medulla oblongata (MeOb) of rat brain. The M1 cholinergic receptor (M1-R) was found to account for approximately 30-40% of the total muscarinic receptors (M-R) in the pons and MeOb, and the M2 accounted for about 60-70%. The receptor binding capacities of scopolamine and atropine were compared with those of pirenzepine (Pir) and AF-DX 116 on the 2 parts of the brain. The affinity values (pKi) suggest that the selectivity of scopolamine for M1-R is greater than for M2-R, and that of atropine for M2 is greater than for M1. In conscious rabbits, the respiratory frequency (FR), tidal volume (TV), and minute ventilation volume (MVV) were determined. Arterial blood samples were taken intermittently and analyzed for pO2, pCO2, and pH. When pilocarpine (a M1-R subtype selective agonist) was given, excitatory effects on respiration were seen through FR, TV, MVV, and the pO2, pCO2, and pH. When 6 beta-acetoxy nortropane (6 beta-AN, a novel M2-R subtype selective agonist) was given, the effects were inhibitory. These results were reversed after administration of Pir, scopolamine, AF-DX 116, and atropine. Thus, it shows that Pir and scopolamine inhibit respiration by blocking the M1-R subtype of the respiratory center, while the excitatory effects of AF-DX 116 and atropine are brought about by blocking the M2-R subtype of the respiratory center.
使用[3H]东莨菪碱和[3H]哌仑西平进行放射受体结合试验，对大鼠脑桥和延髓进行检测。结果发现，M1胆碱能受体（M1-R）约占脑桥和延髓中总毒蕈碱受体（M-R）的30%-40%，M2胆碱能受体约占60%-70%。比较了东莨菪碱和阿托品与哌仑西平（Pir）和AF-DX 116在脑的这两个部位的受体结合能力。亲和力值（pKi）表明，东莨菪碱对M1-R的选择性大于对M2-R的选择性，而阿托品对M2的选择性大于对M1的选择性。对清醒家兔测定呼吸频率（FR）、潮气量（TV）和分钟通气量（MVV）。间歇性采集动脉血样本，分析其中的pO2、pCO2和pH值。给予毛果芸香碱（一种M1-R亚型选择性激动剂）时，通过FR、TV、MVV以及pO2、pCO2和pH值可观察到对呼吸的兴奋作用。给予6β-乙酰氧基去甲托烷（6β-AN，一种新型M2-R亚型选择性激动剂）时，作用为抑制性。给予Pir、东莨菪碱、AF-DX 116和阿托品后，这些结果发生逆转。因此，表明Pir和东莨菪碱通过阻断呼吸中枢的M1-R亚型来抑制呼吸，而AF-DX 116和阿托品的兴奋作用是通过阻断呼吸中枢的M2-R亚型实现的。
