ROLE OF VAGAL FIBERS AND BOMBESIN GASTRIN-RELEASING PEPTIDE-NEURONS IN DISTENSION-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 gastri n release are still a matter of debate. Accordingly, the aim of the pr esent study was to examine the contribution of afferent and efferent v agal fibers as well as intrinsic neurons on gastrin response to gastri c distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent incr ease 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 s tudied in anesthetized rats after bilateral truncal vagotomy (n = 9) o r selective afferent vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin release by 10 mi distention in sham-oper ated control rats was reversed to an inhibition after truncal vagotomy (26+/-7 vs. - 11+/-4 pg/ml; P < 0.05) and capsaicin-treatment (37+/-1 8 vs. - 34+/-11 pg/ml P < 0.05). A contribution of cholinergic mechani sms to this vagovagal-mediated stimulation of distention-induced gastr in release was excluded, since atropine (100 mu g/kg/h; n = 8) further augmented distention-stimulated gastrin release. Since bombesin/gastr in-releasing peptide (GRP)-neurons contribute to vagally stimulated ga strin secretion, we have examined gastrin response to distention in th e presence of the specific bombesin-receptor antagonist D-Phe(6)-BN(6- 13)OMe (400 mu g/kg/h; n = 10). This bombesin-antagonist completely re duced distention-stimulated gastrin release in vivo. In contrast, dist ention 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/mi n (15 ml saline, n = 8, P < 0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastr in release was attenuated to 50 percent by atropine (10(-7) M; it = 10 ) or tetrodotoxin (TTX) (10(-6) M;n = 10), respectively. These data de monstrate, that in anesthetized rats distention-stimulated gastrin sec retion depends on the activation of a vagovagal reflex and intrinsic b ombesin/ GRP-neurons. In contrast distention of the isolated rat stoma ch inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms. (C) 1997 Elsevier Science B.V.