Tanikawa M, Hayakawa T, Kondo T, Naruse S, Shibata T, Kitagawa M
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Digestion. 1994;55(6):374-9. doi: 10.1159/000201168.
The purpose of this study was to determine the regulation of pancreatic polypeptide (PP) release by using pirenzepine (a specific M1 muscarinic receptor antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic receptor antagonist), atropine (a nonspecific muscarinic receptor antagonist), and loxiglumide (cholecystokinin, CCK, receptor antagonist) in dogs. In conscious dogs with chronic gastric and duodenal fistulas, release of PP and exocrine pancreatic secretion were stimulated by constant intravenous infusion of CCK-8 (200 ng/kg/h). Graded doses of pirenzepine (0.18-4.7 mmol/kg/h), 4-DAMP (6.7-180 nmol/kg/h), or atropine (0.89-24 nmol/kg/h) dose-dependently reduced plasma PP responses to CCK-8 without influence on exocrine pancreatic secretion. ID50 calculated from these results were 492 +/- 150 nmol/kg/h for pirenzepine, 10.7 +/- 1.8 nmol/kg/h for 4-DAMP and 19.4 +/- 5.2 nmol/kg/h for atropine. A similar sequence in the inhibitory potency was observed in 2-deoxy-D-glucose (2-DG, 100 mg/kg)-stimulated PP release, exocrine pancreatic, and gastric secretions. On the other hand, loxiglumide, a CCK receptor antagonist, did not influence PP release stimulated by 2-DG. These findings suggest that both CCK- and 2-DG-stimulated PP releases are mainly under cholinergic nerve control mediated by M3 muscarinic receptor in dogs.
本研究的目的是通过使用哌仑西平（一种特异性M1毒蕈碱受体拮抗剂）、4-二苯基乙酰氧基-N-甲基哌啶甲基溴化物（4-DAMP，一种特异性M3毒蕈碱受体拮抗剂）、阿托品（一种非特异性毒蕈碱受体拮抗剂）和洛西格列胺（胆囊收缩素，CCK，受体拮抗剂）来确定犬胰腺多肽（PP）释放的调节机制。在患有慢性胃和十二指肠瘘的清醒犬中，通过持续静脉输注CCK-8（200 ng/kg/h）刺激PP释放和胰腺外分泌。不同剂量的哌仑西平（0.18 - 4.7 mmol/kg/h）、4-DAMP（6.7 - 180 nmol/kg/h）或阿托品（0.89 - 24 nmol/kg/h）剂量依赖性地降低了血浆PP对CCK-8的反应，而对外分泌性胰腺分泌无影响。根据这些结果计算出的哌仑西平的ID50为492±150 nmol/kg/h，4-DAMP为10.7±1.8 nmol/kg/h，阿托品为19.4±5.2 nmol/kg/h。在2-脱氧-D-葡萄糖（2-DG，100 mg/kg）刺激的PP释放、外分泌性胰腺和胃分泌中也观察到了类似的抑制效力顺序。另一方面，CCK受体拮抗剂洛西格列胺不影响2-DG刺激的PP释放。这些发现表明，在犬中，CCK和2-DG刺激的PP释放主要受M3毒蕈碱受体介导的胆碱能神经控制。
