M-胆碱药物对大鼠皮层、腮腺和豚鼠小肠纵肌中 M-乙酰胆碱受体的作用比较

本文应用[~3H]-QNB 为放射性配基,研究 M-胆碱激动剂或阻滞剂对大鼠脑皮层、腮腺和豚鼠小肠纵肌中 M-乙酰胆碱受体竞争结合的影响。经量-效比式计算后,证明它们的作用斜率(b)约为1,表明它们作用在相同的 M-乙酰胆碱受体。阻滞剂对皮层中 M-胆碱受体的抑制结合强度次序为:QNB>阿托品,东莨菪碱>苯海索>M-8218>B-7601>M-8225>7911;而它们对腮腺中 M-乙酰胆碱受体的抑制作用次序有明显不同,即 M-8218>QNB>7911>M-8225>B-7601>苯海索>阿托品>东莨菪碱,其中阿托品和东莨菪碱的抑制结合强度分别为皮层的1/111和1/315。这提示不同靶细胞中的 M-乙酰胆碱受体与相同配基结合时有不同的专一性。试验证明包公藤甲素抑制[~3H]-QNB 的结合作用与毛果芸香碱相似,它们均为激动剂,对受体的亲和力比阻滞剂弱1000倍左右。

COMPARISON OF EFFECTS OF M-CHOLINERGIC COMPOUNDS ON M-ACETYLCHOLINE RECEPTORS IN RAT CORTEX PAROTID GLAND AND LONGITUDINAL MUSCLE FROM SMALL INTESTINE OF GUINEA PIG

[~3H]-QNB was used as a radioligand for M-acetylcholine receptors(M-AChR)binding in the experiments of competitive inhibition by M-cholinergic agonists andantagonists with the homogenate preparations of rat cortex,parotid gland,andlongitudinal muscle from small intestine of guinea pig.With the regression computation(dose-response equation),the slopes of thesecompounds were all approximate to 1.Thus it was indicated that they acted in thesame way on M-AChR(or receptor sites).The rank order of potency of receptorbinding assay(IC_(50))in rat cortex was QNB>atropine,scopolamine>benzhexal>M-8218>B-7601>M-8225>7911,but that in the rat parotid gland was signi-ficantly different,i.e.M-8218>QNB>7911>M-8225>B-7601>benzhexalatropine>scopolamine.In particular,the potencies of atropine and scopola-mine in the rat cortex were 111 and 315.5 times as active respectively as thosein the rat parotid gland.It is,therefore,suggested that M-AChR in the differenttarget organs have some specific characteristics to be found by various M-antagonists.