Muscarinic receptor desensitization and downregulation induced by full and partial cholinergic agonists in rat pancreatic acini.
Muscarinic receptor desensitization and downregulation induced by full and partial cholinergic agonists in rat pancreatic acini.
复制标题
完全和部分胆碱能激动剂在大鼠胰腺腺泡中诱导毒蕈碱受体脱敏和下调。
DOI：
10.1097/00006676-198906000-00007
复制
发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Habara,Y
中科院分区：
文献类型：
--
作者：
Hootman,SR;Kuroiwa,CL;Habara,Y
预孵育大鼠胰腺腺泡与卡巴胆碱，一个完整的胆碱能激动剂，在37 [degree] C的30分钟，导致了几倍的效力降低，这种激动剂引起淀粉酶释放腺泡在随后的30分钟孵育，但没有降低其最大效力。与卡巴胆碱预孵育的腺泡对胆囊收缩素的反应略低，胆囊收缩素利用相同的细胞内信使，但在第二次孵育中对部分胆碱能激动剂毛果芸香碱几乎完全无反应。相比之下，预孵育的腺泡与毛果芸香碱长达120分钟，在37 [度] C未能改变随后的分泌反应本身或卡巴胆碱。胰腺腺泡在含有卡巴胆碱或毛果芸香碱的培养基中孵育长达24 h，可引起细胞表面毒蕈碱胆碱能受体的时间和浓度依赖性降低，通过结合标记的毒蕈碱拮抗剂[3 H] N-甲基东莨菪碱进行评估。这些结果表明，胆碱能脱敏的胰腺腺泡的分泌反应是由受体性质的变化所引起的，而这种变化与从细胞表面清除被占领的受体不同。
Preincubation of rat pancreatic acini with carbachol, a full cholinergic agonist, for 30 min at 37 [degrees] C caused a several-fold decrease in the potency of this agonist to elicit amylase release from acini in a subsequent 30-min incubation, but did not reduce its maximal efficacy. Acini preincubated with carbachol were slightly less responsive to cholecystokinin, which utilizes the same intracellular messengers, but were almost completely unresponsive to the partial cholinergic agonist pilocarpine in a second incubation. In contrast, preincubation of acini with pilocarpine for up to 120 min at 37 [degrees] C failed to alter the subsequent secretory response either to itself or to carbachol. Incubation of pancreatic acini for up to 24 h in a hormonally defined culture medium containing either carbachol or pilocarpine caused a time and concentration dependent decrease in cell surface muscarinic cholinergic receptors, as assessed by binding of the labeled muscarinic antagonist [3H] N-methylscopolamine. These results suggest that cholinergic desensitization of secretory responsiveness in the pancreatic acinus is caused by a change in receptor properties distinct from that which elicits removal of the occupied receptor from the cell surface.