Effect of sumatriptan on external pancreatic secretion and its interactionwith endogenous norepinephrine in the rat

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 niso xetine. Urethane-anesthetized male Wistar rats were fitted with an acute pa ncreatic 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 mu g/kg.h). (i) 2DG: Nisoxetine alone inhibited 2DG-induced pancreatic secretion (p < 0.01). Sumatriptan alone also produced a dose-related inhibi tion of 2DG-induced pancreatic secretion (p < 0.01). When sumatriptan and n isoxetine were combined, protein response to 2DG remained inhibited, wherea s water and electrolyte secretion was restored. (ii) Vagal stimulation: Nis oxetine did not modify water and electrolyte output in response to vagal el ectrical stimulation (VES), whereas it inhibited protein response by 75%. S umatriptan 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 resto red. (iii) Acetylcholine: Nisoxetine and sumatriptan alone or combined did not modify pancreatic response to acetylcholine. These results indicate tha t noradrenergic and serotonergic agents can indirectly affect pancreatic se cretion through a modulation of the vagal cholinergic pathway. Nisoxetine a nd sumatriptan interact negatively on hydroelectrolytic pancreatic secretio n, whereas they inhibit the secretion of enzymes both alone and in combinat ion.