Modulation of external pancreatic secretion by endogenous norepinephrine: Study with a norepinephrine uptake blocker in the rat

The effect of endogenous catecholamines on pancreatic secretion was analyze d with nisoxetine, a specific norepinephrine uptake blocker, and specific a drenoceptor antagonists in anesthetized acute fistula rats. Nisoxetine was administered alone or with alpha-1 (prazosin). alpha-2 (idazoxan or yohimbi ne), or beta (propranolol) adrenoceptor antagonists. pancreatic secretion w as measured in basal conditions or after stimulation by 2-deoxy-D-glucose ( 2DG), electrical vagal stimulation, or acetylcholine. (a) Basal. Nisoxetine alone had no effect. Associated with idazoxan or yohimbine, nisoxetine pro duced a dose-related stimulation (p < 0.01) of water and electrolyte withou t changing protein output. Addition of propranolol abolished this stimulati on. (b) 2DG. Nisoxetine inhibited 2DG-induced secretion (p < 0.01). Idazoxa n or yohimbine suppressed the nisoxetine inhibition of water and electrolyt e output (p < 0.01) but had no effect on protein output, which was restored only by adding a mixture of idazoxan, prazosin, and propranolol. (c) Elect rical stimulation. Nisoxetine did not modify water and electrolyte but inhi bited protein response by 75%. Adding idazoxan to nisoxetine significantly increased (p < 0.01) water and bicarbonate response and partly restored pro tein response. Water and bicarbonate response was restored by propranolol. whereas protein response was only restored by adding a mixture of idazoxan, prazosin, and propranolol. (d) Nisoxetine did not modify pancreatic respon se to acetylcholine. In conclusion, endogenous norepinephrine affects the r esponse to vagally mediated effects through several subtypes of adrenocepto rs, without changing basal or acetylcholine stimulated secretion.