Effects of cyclooxygenase-2 inhibitor on glucagon-induced delayed gastric emptying and gastric dysrhythmia in dogs

The objective of this study was to investigate the effects of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on delayed gastric emptying and gastric dysrhythmia induced by glucagon. The study was performed in six healthy female dogs implanted with four pairs of gastric serosal electrodes, and a duodenal fistula for the assessment of gastric emptying. Each dog was studied in three randomized sessions: control, glucagon and COX-2 inhibitor (celecoxib). Gastric emptying was assessed every 15 min via a duodenal cannula by calculating the amount of collected phenol red which mixed with the test meal and gastric slow waves were recorded at the same time. We found that: (i) glucagon significantly and substantially decreased gastric emptying of liquids (P < 0.001, ANOVA), increased blood glucose (BG) levels, and induced gastric dysrhythmias. The delayed gastric emptying was correlated with the BG level (R = -0.77, P < 0.001) and (ii) celecoxib improved glucagon-induced delayed gastric emptying at 30, 45, 60 and 75 min after feeding. Celecoxib did not blocked dysrhythmic action of glucagon (P > 0.05, ANOVA). In conclusion, glucagon induces delayed gastric emptying partially via COX-2-derived prostaglandins. However, COX-2-derived prostaglandins are not involved in glucagon-evoked gastric dysrhythemia. Selective COX-2 inhibitors may provide a possible therapeutic option for diabetic gastroparesis.