Goepel M, Gronewald A, Krege S, Michel M C
Department of Urology, University of Essen Medical School, Germany.
Urol Res. 1998;26(2):149-54. doi: 10.1007/s002400050038.
The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and female pigs and in humans (Kd = 35 +/- 8 pM, Bmax = 153 +/- 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine >> hexahydro-sila-difenidol > or = AF-DX 116 > or = pirenzepine, indicating the presence of a homogeneous population of M2 muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of alpha2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M2 subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression.
在以[3H]喹核醇基苯甲酸酯作为放射性配体的放射配体结合研究中，比较了猪和人膀胱逼尿肌毒蕈碱型乙酰胆碱受体的特性。雄性和雌性猪以及人类中，放射性配体与受体的亲和力和毒蕈碱受体密度相似（解离常数Kd = 35 ± 8皮摩尔，最大结合容量Bmax = 153 ± 30飞摩尔/毫克蛋白质）。阿托品和亚型选择性拮抗剂在猪和人逼尿肌中具有陡峭的单相竞争曲线，其效价顺序为阿托品 >> 六氢硅二苯哌啶 ≥ AF-DX 116 ≥ 哌仑西平，表明存在均一的M2毒蕈碱受体群体。在雌性猪中，部分尿道结扎导致的膀胱流出道梗阻或通过回肠扩大术或自身扩大术进行的手术治疗，并未显著改变毒蕈碱受体或α2A肾上腺素能受体的表达，但检验效能不足以排除小于60%的改变。我们得出结论，猪和人逼尿肌表达M2亚型的毒蕈碱受体；尽管在性质上有这些相似之处，但猪模型的应用可能会因受体表达量方面的巨大生物学差异而受到限制。
