Capsaicin-sensitive vagal fibres and 5-HT3-, gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibitionof gastric emptying in the rat

The present study was undertaken to investigate how the activation of gastr ic mechanoreceptors by distension of the stomach in conscious gastric fistu la rats influences gastric emptying; and the roles of capsaicin sensitive v agal afferent fibres and the 5-HT3, GRP and CCK-A receptors involved in med iating these responses. To activate mechanoreceptors by non-nutrient depend ent pathways, methylcellulose in saline was used to distend the stomach (5 cm H2O) and the subsequent emptying of saline was examined immediately, and at 3, 5 and 10 min following distension. Prior distension delayed the subs equent emptying of saline instilled into the stomach compared with non-dist ended controls (2.28+/-0.09 m1/5 min; P<0.001). Topical application of caps aicin, completely abolished the distension-induced inhibition of gastric em ptying when compared with vehicle treated rats (2.82+/-0.09 vs. 2.38+/-0.04 m1/5 min; P < 0.001). Peripheral administration of a CRP antagonist (2258 U89UJ, 1 mg/kg), and a 5-HT3 antagonist (BRL4369UA, 50 mu g/kg) significant ly reversed (2.56+/-0.14 m1/5 min; P < 0.05 and 2.61+/-0.07 m1/5 min; P < 0 .01; respectively) the delay in gastric emptying induced by distension. Whe n the rats were treated with the CCK-A antagonist, gastric emptying of sali ne following distension was also significantly facilitated (2.56+/-0.07 m1/ 5 min; P < 0.001). In contrast, the CCK-B/gastrin receptor antagonist had n o significant effect pn the distension induced delay in gastric emptying (1 .95+/-0.12 m1/5 min). The present results suggest that gastric distension i n conscious gastric fistula rats delays gastric emptying by activating caps aicin-sensitive extrinsic afferent nerve fibres. Moreover, the results also indicate that distension-induced mechanisms involve GRP, 5-HT3 and CCK-A r eceptors, but not CCK-B receptors. (C) 1999 Elsevier Science BN. All rights reserved.