Development of muscarinic m_3 and m_4 receptor antibodies with pharmacological activities

• 作 者: 王海鹰 曾淑君 邱鹏新
• 机 构: 中山医科大学药理教研室
• 出 处: Acta Pharmacologica Sinica
• 发表日期: 1998年06期
• 关键词: 受体功能 动脉环 大脑皮质 胸主动脉 毒蕈碱受体 受体结合 抑制率 舒张作用 配基 配位体

目的：探讨制备具有药理活性的亚型选择性抗受体抗体和以其研究受体功能的可行性．方法：合成ｍ３与ｍ４受体亚型特异的多肽免疫兔制备抗体；放射配位体测定研究抗体对Ｍ受体配基结合的影响．研究抗体对乙酰胆碱的回肠收缩与动脉环舒张作用的影响．结果：制备成抗ｍ３与ｍ４受体的抗体．ｍ３抗体对［３Ｈ］ＱＮＢ与大鼠大脑皮质、心肌、及唾液腺（颌下腺及腮腺）Ｍ受体结合最大抑制率分别为１２１％±２１％、１５７％±１１％与６３６％±２８％，ｍ４抗体则分别为２８％±６％、１９３％±２６％与１６％±１４％．ｍ３抗体抑制乙酰胆碱的回肠收缩与动脉环舒张．结论：制备具有药理活性的亚型选择性抗受体抗体并用以研究受体功能是可行的

OBJECTIVE: To investigate the feasibility of preparing subtype selective anti-receptor antibodies with pharmacological activity and to study the function of receptors. Methods: Antibodies were prepared from immunized rabbits with specific mimic of m4 and m4 receptor subtypes. Radioligand assay was used to study the effect of antibody on M receptor ligand binding. To study the effect of antibody on the ileal contraction and arterial ring relaxation of acetylcholine. Results: The anti-m3 and m4 receptor antibodies were prepared. m3 antibody inhibited the binding of [3H] QNB to M receptor in cerebral cortex, myocardium and salivary gland (submandibular gland and parotid gland) in rats by 121% ± 21% and 157% ± 11% And 636% ± 28%, respectively. The levels of m4 antibody were 28% ± 6%, 193% ± 26% and 16% ± 14%, respectively. m3 antibody inhibits the ileal contraction of acetylcholine and arterial ring relaxation. CONCLUSIONS: It is feasible to prepare subtype selective anti-receptor antibodies with pharmacological activity and to study receptor function