MECHANISM OF INHIBITORY EFFECT OF GLUCAGON ON GASTROINTESTINAL MOTILITY AND CAUSE OF SIDE-EFFECTS OF GLUCAGON

Glucagon is commonly used during gastrointestinal examinations for the temporary inhibition of gastroduodenal movements. Three preparations of glucagon are now clinically available: those prepared by extraction from the pancreas (GL-P), by chemical synthesis (GL-S), and by geneti c recombination (GL-G). The aim of this study was examine the mechanis m of the inhibitory effect of glucagon on gastrointestinal motility an d the cause of its side effects by comparing three glucagon preparatio ns. In four conscious dogs, gastrointestinal contractions were monitor ed by means of chronically implanted force transducers. Each glucagon preparation (GL-P [15 mu g/kg], GLS [5, 15, 45 mu g/kg], GL-G [15 mu g /kg]), scopolamine butylbromide (0.4 mg/kg), or saline was administere d intravenously 20 min after the termination of spontaneous phase III contractions, and blood samples were taken at 5- to 10-min intervals. Barium was administered into the stomach 10 min after the infusion of each drug. The arrival of a barium meal in the stomach immediately sti mulated gastrointestinal contractions, and the barium meal was expelle d into the duodenum and jejunum from the stomach. Intravenous injectio n of 15 mu g GL-S first stimulated duodenal contractions that propagat ed to the jejunum, followed by strong inhibition of the barium-induced gastrointestinal contractions. This inhibitory effect of glucagon and the activity of the glucagon-induced duodenal contractions were dose- related. The inhibitory effects of GL-G and GL-S were stronger than th at of GL-P. Blood glucose and plasma insulin concentrations were raise d after intravenous injection of each glucagon preparation, but there was no difference among the three preparations and no dose relationshi p. The inhibitory effects of glucagon depend on the material purity an d dose, and the inhibitory mechanism was independent of any effect on carbohydrate metabolism. Glucagon administration caused phase III-like contractions in the duodenum and jejunum, which may be responsible fo r the side effects of glucagon.