ROLE OF 5-HT3 RECEPTORS IN THE CONTROL BY CHOLECYSTOKININ OF TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXATIONS IN DOGS

Aims. - The aim of this study was to determine, using specific antagon ists, whether 5-HT3 receptors participate in triggering transient lowe r esophageal sphincter relaxations, independently or in relation with their CCKergic control. Methods. - Esophageal, lower esophageal sphinc ter and fundus pressure were manometrically monitored in 5 conscious d ogs. Gastric distensions with air at constant pressure (1.0 and 1.7 kP a) were performed during 30 min under IV infusion of CCK8S (0.5 mu g/k g/h) or NaCl 9 parts per thousand and were preceded (10 min) by IV adm inistration of 5-HT3 receptors antagonists (ondansetron 0.2-500 mu g/k g and granisetron 100 mu g/kg) or NaCl 9 parts per thousand. Results. - The number of transient relaxations induced by a 1.7 kPa gastric dis tension (7.9 +/- 0.4/30 min) was dose-dependently reduced by ondansetr on (1-100 mu g/kg) and by granisetron (100 mu g/kg). Ondansetron (100 mu g/kg) did not modify the number of relaxations under a 1.0 kPa gast ric pressure (2.7 +/- 0.4 vs 2.6 +/- 0.4/30 min) but reduced the incre ase of the occurrence of relaxations induced by CCK8S under a gastric pressure of 1.0 and 1.7 kPa. Conclusion. - These results suggest that the CCK control in triggering transient lower esophageal sphincter rel axations is modulated by serotonin via 5-HT3 receptors subtypes.