Gastrin-Releasing Peptide Facilitates Cholinergically Mediated Contractions of the Mouse Gastric Fundus

Gastrin-releasing peptide (GRP) and neuromedin B (NMB) are found in the stomach's myenteric plexus and muscular layers. When exogenously administered, they contract stomach muscle in several species, but their ability to modulate enteric nerve functions has rarely been studied. We investigated the effects of GRP on cholinergic-mediated contractions of the stomach, after first characterizing the contractile effects of GRP, NMB, and bombesin (BB). Circular muscle rings, cut from the mouse gastric fundus, were studied using tissue bath techniques. Contractions evoked by electrical field stimulation (EFS; 5 Hz) were examined under non-adrenergic, non-nitrergic conditions. Contractions were expressed as % of the maximum contraction induced by carbachol (100 μM). GRP (0.0001-1 μM), NMB (0.0001-3 μM), and BB (0.0001-1 μM) induced concentration-dependent tonic muscle contractions. The pD₂ and E_max were, respectively, GRP: 7.2 ± 0.1, 54.6% ± 3.6% (n = 14); BB: 7.4 ± 0.2, 47.2% ± 3.9% (n = 9); and NMB: 6.3 ± 0.1, 38.1% ± 5.6% (n = 10). GRP- and NMB-induced contractions were inhibited by the BB₂ receptor antagonist BW-10, not by the BB₁ receptor antagonist PD168368. EFS-evoked contractions were blocked by atropine (1 μM) or tetrodotoxin (1 μM), and concentration-dependently potentiated by GRP (0.0001-1 μM), with pD₂ and E_max values 7.8 ± 0.1 and 81.2% ± 14.0%, respectively (n = 17). This activity was inhibited by BW-10, not PD168368. BW-10 alone also reduced EFS-evoked contraction amplitudes. GRP and BW-10 did not affect contractions induced by bethanechol (1-300 μM). In conclusion, in mouse gastric fundus, GRP causes muscle contraction and also facilitates electrically evoked cholinergic activity (facilitating ACh release), both actions most likely involving BB₂ receptor activation. Further experiments must ascertain the physiological significance of these actions, alone and together.