Gies J P, Bertrand C, Vanderheyden P, Waeldele F, Dumont P, Pauli G, Landry Y
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur-Strasbourg, France.
J Pharmacol Exp Ther. 1989 Jul;250(1):309-15.
Muscarinic receptor subtypes in human, guinea pig and rat lung tissue were characterized by radioligand binding, and functional studies were carried out on guinea pig and rat tissues. Control binding experiments were performed with membranes from human tissues rich in M1 (hippocampus), M2 (pons-medulla) and M3 (salivary gland) receptor subtypes. Competitive binding experiments with atropine and 4-diphenylacetoxy-N-methylpiperidine methobromide did not reveal any tissue selectivity of these ligands. Pirenzepine, a selective M1 antagonist with 11-2[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido[2,3-b] [1,4]-benzodiazepine-6-one (AF-DX116), a selective M2 antagonist, made it possible to characterize muscarinic subtypes. In hearts from the three species, the low affinity for pirenzepine and the high affinity for AF-DX116 were related to M2 receptors. In rat lung, the high affinity for AF-DX116 and the intermediate affinity for pirenzepine indicate M2 and M3 subtypes. Guinea pig and human lung tissues contain 48 and 67%, respectively, of muscarinic binding sites with high affinity for pirenzepine (M1). The second muscarinic receptor population in human lung might be classified as M3 in view of the cardioselectivity of AF-DX116, but the occurrence of M2 cardiac-type receptors could not be excluded. In guinea pig lung, both M2 and M3 subtypes might occur in addition to M1 receptors. Muscarinic stimulation led to the contraction of guinea pig and rat lung strips but did not significantly affect human lung strips. We suggest that presynaptic M2-muscarinic receptors modulated the M3-induced contraction in the guinea pig lung smooth muscle.
通过放射性配体结合对人、豚鼠和大鼠肺组织中的毒蕈碱受体亚型进行了表征，并对豚鼠和大鼠组织进行了功能研究。使用富含M1（海马体）、M2（脑桥-延髓）和M3（唾液腺）受体亚型的人体组织膜进行对照结合实验。用阿托品和4-二苯基乙酰氧基-N-甲基哌啶甲基溴进行的竞争性结合实验未揭示这些配体的任何组织选择性。哌仑西平，一种选择性M1拮抗剂，以及11-2[[2-[(二乙氨基)甲基]-1-哌啶基]乙酰基]-5,11-二氢-6H-吡啶并[2,3-b][1,4]-苯二氮䓬-6-酮（AF-DX116），一种选择性M2拮抗剂，使得对毒蕈碱亚型进行表征成为可能。在这三个物种的心脏中，对哌仑西平的低亲和力和对AF-DX116的高亲和力与M2受体有关。在大鼠肺中，对AF-DX116的高亲和力和对哌仑西平的中等亲和力表明存在M2和M3亚型。豚鼠和人肺组织分别含有48%和67%对哌仑西平（M1）具有高亲和力的毒蕈碱结合位点。鉴于AF-DX116的心脏选择性，人肺中的第二个毒蕈碱受体群体可能归类为M3，但不能排除M2心脏型受体的存在。在豚鼠肺中，除M1受体外，可能还存在M2和M3亚型。毒蕈碱刺激导致豚鼠和大鼠肺条收缩，但对人肺条没有显著影响。我们认为突触前M2-毒蕈碱受体调节了豚鼠肺平滑肌中M3诱导的收缩。
