Inhibition of pancreatic protein secretion by ghrelin in the rat

1. The role of ghrelin in the regulation of pancreatic protein secretion wa s investigated in vivo using anaesthetized rats with pancreatic ductal cann ulas, and in isolated pancreatic acinar cells and pancreatic lobules in vit ro. indirect and may be exerted at the level of intrapancreatic neurons. 2. In vivo, pancreatic protein output stimulated by CCK-8 (400 pmol kg(-1) h(-1)) was dose-dependently inhibited by continuous ghrelin infusion (1.2 a nd 12 nmol kg(-1) h(-1)) by 45 +/- 8 and 84 +/- 7%, respectively. 3. In rats with acute subdiaphragmatic vagotomy, ghrelin (12 nmol kg(-1) h( -1)) significantly inhibited CCK-stimulated pancreatic protein secretion by 75 +/- 18%. 4. Infusion of ghrelin (12 nmol kg(-1) h(-1)) abolished pancreatic protein secretion caused by the central vagal stimulant 2-deoxy-D-glucose (75 mg kg (-1)), whereas bethanechol-stimulated pancreatic protein output was inhibit ed by only 59 +/- 7%. 5. In vitro, ghrelin (10(-11)-10(-7) M) produced no change in basal amylase release from dispersed, purified acinar cells. Co-incubation of ghrelin (1 0(-11)-10(-7) M) with CCK-8 (10(-10) M) demonstrated no inhibition of CCK-s timulated amylase release from dispersed acini. In contrast, ghrelin (10(-9 )-10(-7) M) dose-dependently inhibited amylase release from pancreatic lobu les exposed to 75 rum potassium. 6. Our results show that (1) ghrelin is a potent inhibitor of pancreatic ex ocrine secretion in anaesthetized rats in vivo and in pancreatic lobules in vitro; and (2) the actions of ghrelin are indirect and may be exerted at t he level of intrapancreatic neurons.