Weigert N, Li Y Y, Lippl F, Coy D H, Classen M, Schusdziarra V
Department of Internal Medicine II, Technical University of Munich, Germany.
Neuropeptides. 1996 Dec;30(6):521-7. doi: 10.1016/s0143-4179(96)90033-5.
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.
外源性蛙皮素及其相关的哺乳动物肽对胃酸分泌和胃泌素释放的刺激作用已得到详细研究，而内源性释放的类蛙皮素肽的调节作用在很大程度上尚不清楚。因此，我们确定了一种特异性蛙皮素受体拮抗剂在迷走神经刺激胃酸分泌和胃泌素释放过程中的作用。在麻醉大鼠中，电刺激迷走神经（10V，10Hz，1ms）可使血浆胃泌素水平显著升高82±11pg/20min（P<0.01），胃酸分泌量增加99.4±9.9μeq/20min（P<0.01）。静脉输注特异性蛙皮素受体拮抗剂D-Phe6-BN(6-13)OMe（400nmol/kg/h）可使迷走神经诱导的血浆胃泌素水平升高显著降低70%，降至29±8pg/20min（与对照组相比P<0.05），并使迷走神经刺激的胃酸分泌量降低40%，降至57.4±10.6μeq/20min（与对照组相比P<0.05）。为了证明残余的胃泌素和酸反应是由于非蛙皮素能机制而非受体拮抗剂剂量不足所致，在最大有效浓度300pmol/kg/h下，将该拮抗剂与胃泌素释放肽（GRP）进行了对比试验，结果显示与迷走神经刺激相比，GRP使血浆胃泌素水平升高幅度甚至高出50%。所采用的拮抗剂剂量（400nmol/kg/h）足以消除GRP诱导的胃泌素和胃酸分泌刺激。此前曾推测内源性蛙皮素肽可通过非胃泌素依赖机制刺激胃酸分泌。为进一步研究这种可能性，在胃泌素水平恢复到各自对照实验范围内时，研究了拮抗剂对迷走神经诱导的胃酸分泌的影响。在存在拮抗剂的情况下，除迷走神经刺激外输注胃泌素-17（15pmol/kg/h）可使血浆胃泌素升高至与单纯迷走神经刺激时无差异的水平。在血浆胃泌素水平相同的情况下，蛙皮素受体拮抗剂对迷走神经刺激的胃酸分泌无影响（86.3±10.7μeq/20min，对照组为99.4±9.9μeq/20min；无显著差异）。总之，目前的数据首次证明，在体内大鼠中，内源性蛙皮素肽有助于迷走神经刺激胃泌素释放和胃酸分泌。此外，内源性蛙皮素肽通过增加胃泌素释放对壁细胞功能发挥作用，而在所用实验条件下，非胃泌素能机制并不重要。
