Larose L, Leclerc L, Asselin J, Ruel S, Morisset J
Centre de Recherche sur les Mécanismes de Sécrétion, Université de Sherbrooke, Québec, Canada.
Pancreas. 1989;4(1):71-8. doi: 10.1097/00006676-198902000-00011.
In this study, dispersed rat pancreatic acini exhibited secretin subsensitivity in their capacity to release amylase after preexposure to increasing concentrations of the muscarinic cholinergic agonist carbamylcholine. The present study also explores the potential mechanisms involved in this cellular desensitization phenomenon. Secretin subsensitivity of pancreatic acini pre-exposed to 10(-4) M carbamylcholine was observed only at secretin concentrations above 10(-8) M. The desensitized cells had not recovered 3 h after the cholinergic agonist exposure. In these acini, the adenylate cyclase pathway remained unaltered because cholera toxin, forskolin, and 8-Br-cAMP still induced weak, but normal, amylase release when compared with control acini. In vivo administration of pertussis toxin failed to protect the dispersed pancreatic acini against carbamylcholine-induced secretin subsensitivity. Moreover, cAMP production by these acini in response to secretin, cholera toxin, and forskolin was similar to that observed in control acini. Secretin stimulation of inositol phosphate (InsP1, InsP2, InsP3) production after carbamylcholine pre-exposure remained equivalent to that observed in acini that had never been exposed to the cholinergic agonist. Thus, after muscarinic cholinergic agonist exposure, pancreatic acini showed secretin subsensitivity in their capacity to release enzyme. This phenomenon appears to result from modifications at post-second messenger loci.
在本研究中，预先暴露于浓度递增的毒蕈碱胆碱能激动剂氨甲酰胆碱后，分散的大鼠胰腺腺泡在释放淀粉酶的能力方面表现出对促胰液素的反应性降低。本研究还探讨了这种细胞脱敏现象所涉及的潜在机制。仅在促胰液素浓度高于10(-8)M时，才观察到预先暴露于10(-4)M氨甲酰胆碱的胰腺腺泡对促胰液素的反应性降低。胆碱能激动剂暴露3小时后，脱敏细胞仍未恢复。在这些腺泡中，腺苷酸环化酶途径未发生改变，因为与对照腺泡相比，霍乱毒素、福斯可林和8-溴-cAMP仍能诱导微弱但正常的淀粉酶释放。体内给予百日咳毒素未能保护分散的胰腺腺泡免受氨甲酰胆碱诱导的促胰液素反应性降低的影响。此外，这些腺泡对促胰液素、霍乱毒素和福斯可林的cAMP生成与对照腺泡中观察到的相似。预先暴露于氨甲酰胆碱后，促胰液素刺激的肌醇磷酸（InsP1、InsP2、InsP3）生成仍与从未暴露于胆碱能激动剂的腺泡中观察到的相当。因此，在毒蕈碱胆碱能激动剂暴露后，胰腺腺泡在释放酶的能力方面表现出对促胰液素的反应性降低。这种现象似乎是由第二信使后位点的修饰引起的。
