RELATIONSHIPS BETWEEN GASTRIC-MOTILITY AND GASTRIC VAGAL AFFERENT RESPONSES TO CCK AND GRP IN RATS DIFFER

The brain-gut peptides cholecystokinin (CCK) and the mammalian bombesi n-like peptide gastrin-releasing peptide (GRP) suppress food intake. V agotomy blocks CCK- but not bombesin (BN)-induced feeding suppression, demonstrating differential vagal contributions. We examined the relat ionship between the ability of CCK and the active fragment of GRP, GRP -(18-27), to stimulate gastric vagal afferent activity and their abili ty to elicit changes in gastric motility. We also examined ligated cer vical vagal segments and revealed specific I-125-CCK vagal binding wit hout evidence of radiolabeled BN binding sites. Both close arterial an d intraperitoneal CCK and GRP-(18-27) produced dose-dependent increase s in activity in gastric vagal mechanoreceptive afferents. CCK dose de pendently decreased gastric pressure without altering antral wall tens ion, whereas GRP-(18-27) dose dependently increased both gastric press ure and peak antral wall muscle tension. These results suggest that GR P-(18-27) activates gastric vagal afferents secondary to its stimulati on of gastric motor effects. CCK activates this same population of vag al afferents independent of changes in gastric tension, suggesting a d irect action of CCK at functional vagal CCK receptors.