Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distention-induced gastrin release in rats.

In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12+/-6 pg/ml (5 ml saline, n = 8, P =0.05), 26+/-7 pg/ml (10 ml saline, n = 10, P < 0.05) and 37+/-7 pg/ml (15 ml saline, n = 8, P < 0.01 ), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy (n = 9) or selective afferent vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26+/-7 vs. -11+/-4 pg/ml; P<0.05) and capsaicin-treatment (37+/-18 vs. -34+/-11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 microg/kg/h; n = 8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist D-Phe6-BN(6-13)OMe (400 microg/kg/h: n = 10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo. In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13+/-5 pg/min (5 ml saline, n = 8, P < 0.05), 28+/-8 pg/min (10 ml saline, n = 11, P < 0.05) and 35+/-10 pg/min (15 ml saline, n = 8, P < 0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10(-7) M: n = 10) or tetrodotoxin (TTX) (10(-6) M; n = 10), respectively. These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.