Exogenous cholecystokinin‐8 reduces vagal efferent nerve activity in rats through CCKA receptors

It has been proposed that the vagus nerve plays a role in mediating cholecystokinin‐8 (CCK‐8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague‐Dawley rats was recorded. Intravenous infusion of CCK‐8 (0.1–1 nmol) suppressed the efferent activity. The effect of CCK‐8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy. Intravenous infusion of CCKA receptor antagonist L‐364,718 (1–100×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK‐8, but the CCKB receptor antagonist L‐365,260 (1–100×10−6 g) did not in the conditions of either partial or total vagotomy. Intracisternal infusion of L‐364,718 (1×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK‐8 i.v. Infusion of exogenous CCK‐8 did not affect the activity of supradiaphragmatic vagal afferents. The results suggest that the effect of systemically administered CCK‐8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCKA receptors. British Journal of Pharmacology (2000) 129, 1649–1654; doi:10.1038/sj.bjp.0703270