Effect of Sumatriptan on External Pancreatic Secretion and Its Interaction with Endogenous Norepinephrine in the Rat

Abstract

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 mgkg, i.v.) and sumatriptan (0.1-1 mgkg, s.c.) were administered alone or in combination. Pancreatic secretion was measured under stimulation by 2-deoxy-D-glucose (2DG; 75 mgkg, i.v.), by vagal electrical stimulation (4 V, 2 ms, 10 Hz), or by acetylcholine (661,800 pg/kg.h). (i) 2DG: Nisoxetine alone inhibited 2DG-induced pancreatic secretion (p < 0.01 ). Sumatriptan alone also produced a dose-related inhibition of 2DGinduced 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.

Roles of Non-cholinergic Intrapancreatic Nerves, Serotonergic Nerves, on Pancreatic Exocrine Secretion in the Isolated Perfused Rat Pancreas

“…Similarly, spiperone hydrochloride-induced pancreatic exocrine secretion was partially inhibited by atropine in this study. These results agree with previous reports that 5-HT1 receptor agonist produced a dose-related inhibition of pancreatic exocrine secretion through a modulation of the vagal cholinergic pathway [15]. On the other hand, it is reported that 5-HT2 and 5-HT3 receptor antagonists inhibited pancreatic exocrine secretion [16].…”