title: Role of endogenous bombesin-peptides during vagal stimulation of gastric acid secretion in the rat.
abstract: The stimulatory effect of exogenous bombesin and its related mammalian peptides on gastric acid secretion and gastrin release has been examined in detail, while the regulatory role of endogenously released bombesin-like peptides is largely unknown. Accordingly we have determined the effect of a specific bombesin receptor antagonist during vagal stimulation of gastric acid secretion and gastrin release. In anesthetized rats electrical stimulation of the vagal nerves (10 V, 10 Hz, 1 ms) significantly increased plasma gastrin levels by 82 +/- 11 pg/20 min (P < 0.01) and gastric acid output by 99.4 +/- 9.9 mueq/20 min (P < 0.01). Intravenous infusion of the specific bombesin receptor antagonist D-Phe6-BN(6-13)OMe (400 nmol/kg/h) significantly reduced vagally induced increase of plasma gastrin levels by 70% to 29 +/- 8 pg/20 min (P < 0.05 vs control) and vagally stimulated gastric acid output by 40% to 57.4 +/- 10.6 mueq/20 min (P < 0.05 vs control). To demonstrate that the residual gastrin and acid response is due to non-bombesinergic mechanisms and not to an inadequate dose of the receptor antagonist, the latter was tested against gastrin-releasing peptide (GRP) at the maximally effective concentration of 300 pmol/kg/h, which resulted in an even 50% higher increase of plasma gastrin levels compared to vagal stimulation. The dose of the antagonist employed (400 nmol/kg/h) was sufficient to abolish GRP-induced stimulation of gastrin and gastric acid secretion. Previously it has been postulated that endogenous bombesin-peptides can stimulate acid secretion via gastrin-independent mechanisms. To investigate this possibility further the effect of the antagonist was examined on vagally induced acid secretion while gastrin levels were restored to the range of the respective control experiments. In presence of the antagonist the infusion of gastrin-17 (15 pmol/kg/h) in addition to vagal stimulation elevated plasma gastrin to levels not different from those during vagal stimulation alone. With identical plasma gastrin levels the bombesin receptor antagonist had no effect on vagally stimulated acid secretion (86.3 +/- 10.7 mueq/20 min vs 99.4 +/- 9.9 mueq/20 min in the controls; n.s.). In conclusion, the present data demonstrate for the first time that in rats in vivo endogenous bombesin peptides contribute to vagal stimulation of gastrin release and gastric acid secretion. Furthermore, endogenous bombesin-peptides exert their action on parietal cell function via an increase of gastrin release, while non-gastrinergic mechanisms are unimportant under the experimental conditions employed.
authors.affiliation: Department of Internal Medicine II, Technical University of Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Weigert
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Lippl
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
authors.forename: M
authors.initials: M
authors.lastname: Classen
authors.forename: V
authors.initials: V
authors.lastname: Schusdziarra
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000008:administration & dosage / Q000097:blood* / Q000187:drug effects; D006728:Hormones / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D005755:Gastrins; D006728:Hormones; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; C071101:bombesin (6-13), Phe(6) methyl ester-; C013550:gastrin 17; D019886:Gastrin-Releasing Peptide; D001839:Bombesin