Nagain-Domaine C, Presset O, Chariot J, Rozé C
INSERM U410, Faculté de Médecine Xavier Bichat, Paris, France.
Pancreas. 1999 Jul;19(1):56-61. doi: 10.1097/00006676-199907000-00009.
We reported previously that blocking norepinephrine reuptake by nisoxetine could modulate external pancreatic secretion in the rat. We report in this study the interaction of serotonin (5-HT) with endogenous catecholamines by using sumatriptan, an agonist of 5-HT1 receptors, in combination with nisoxetine. Urethane-anesthetized male Wistar rats were fitted with an acute pancreatic fistula. Nisoxetine (0.3 mg/kg, i.v.) and sumatriptan (0.1-1 mg/kg, s.c.) were administered alone or in combination. Pancreatic secretion was measured under stimulation by 2-deoxy-D-glucose (2DG; 75 mg/kg, i.v.), by vagal electrical stimulation (4 V, 2 ms, 10 Hz), or by acetylcholine (60-1,800 microg/kg.h). (i) 2DG: Nisoxetine alone inhibited 2DG-induced pancreatic secretion (p < 0.01). Sumatriptan alone also produced a dose-related inhibition of 2DG-induced pancreatic secretion (p < 0.01). When sumatriptan and nisoxetine were combined, protein response to 2DG remained inhibited, whereas water and electrolyte secretion was restored. (ii) Vagal stimulation: Nisoxetine did not modify water and electrolyte output in response to vagal electrical stimulation (VES), whereas it inhibited protein response by 75%. Sumatriptan alone strongly inhibited pancreatic response to VES (p < 0.01). When nisoxetine and sumatriptan were combined, the protein response to VES remained inhibited, whereas water and electrolyte response to VES was restored. (iii) Acetylcholine: Nisoxetine and sumatriptan alone or combined did not modify pancreatic response to acetylcholine. These results indicate that noradrenergic and serotonergic agents can indirectly affect pancreatic secretion through a modulation of the vagal cholinergic pathway. Nisoxetine and sumatriptan interact negatively on hydroelectrolytic pancreatic secretion, whereas they inhibit the secretion of enzymes both alone and in combination.
我们之前报道过，尼索西汀阻断去甲肾上腺素再摄取可调节大鼠的胰腺外分泌。在本研究中，我们报告了使用5-羟色胺1受体激动剂舒马曲坦与尼索西汀联合使用时，血清素（5-HT）与内源性儿茶酚胺的相互作用。用乌拉坦麻醉的雄性Wistar大鼠安装急性胰瘘。单独或联合给予尼索西汀（0.3mg/kg，静脉注射）和舒马曲坦（0.1-1mg/kg，皮下注射）。在2-脱氧-D-葡萄糖（2DG；75mg/kg，静脉注射）、迷走神经电刺激（4V，2ms，10Hz）或乙酰胆碱（60-1800μg/kg·h）刺激下测量胰腺分泌。（i）2DG：单独使用尼索西汀可抑制2DG诱导的胰腺分泌（p<0.01）。单独使用舒马曲坦也产生了剂量相关的2DG诱导的胰腺分泌抑制作用（p<0.01）。当舒马曲坦和尼索西汀联合使用时，对2DG的蛋白质反应仍然受到抑制，而水和电解质分泌得以恢复。（ii）迷走神经刺激：尼索西汀不改变对迷走神经电刺激（VES）的水和电解质输出，而抑制蛋白质反应达75%。单独使用舒马曲坦强烈抑制胰腺对VES的反应（p<0.01）。当尼索西汀和舒马曲坦联合使用时，对VES的蛋白质反应仍然受到抑制，而对VES的水和电解质反应得以恢复。（iii）乙酰胆碱：单独或联合使用尼索西汀和舒马曲坦均不改变胰腺对乙酰胆碱的反应。这些结果表明，去甲肾上腺素能和血清素能药物可通过调节迷走胆碱能途径间接影响胰腺分泌。尼索西汀和舒马曲坦对胰腺水电解质分泌有负性相互作用，而它们单独或联合使用均抑制酶的分泌。
